RARE DISEASE
Polymyositis
Polymyositis
Polymyositis
Drug discovery
6
drugs
With orphan designations
Overview
Polymyositis (PM) is a rare idiopathic inflammatory myopathy characterized by autoimmune-mediated skeletal muscle inflammation, leading to progressive symmetric proximal muscle weakness. Symptoms include difficulty climbing stairs, rising from seated positions, dysphagia, and fatigue. Systemic complications may involve interstitial lung disease, cardiomyopathy, or arthritis. Diagnosis requires clinical evaluation, elevated muscle enzymes (e.g., CK), electromyography, MRI, and muscle biopsy [1][5][13].
Population
Prevalence: 5–22 cases per 100,000 individuals globally, with peak incidence in adults aged 50–70 [2][4].
Gender: Female predominance (2:1 ratio), higher prevalence in African Americans [17][12].
Comorbidities: Associated with malignancies (e.g., lung, breast) and connective tissue diseases (e.g., lupus, scleroderma) [9][11].
Burden
Survival: 75% 5-year survival (PM) vs. 63% (dermatomyositis); median survival 11–12 years [2][4].
Complications: Respiratory failure, dysphagia-related aspiration, and malignancy-driven mortality [9][17].
Healthcare impact: High disability rates, prolonged immunosuppressive therapy, and frequent hospitalizations [9][19].
Therapies
First-line: High-dose corticosteroids (prednisone) ± steroid-sparing immunosuppressants (methotrexate, azathioprine) [3][8].
Refractory cases: Biologics (rituximab), IV immunoglobulin, or mycophenolate mofetil [3][18].
Supportive care: Physical therapy to preserve muscle function and multidisciplinary management for dysphagia/respiratory involvement [3][13].
Categories: rare neurological diseases, rare renal diseases, rare systemic and rheumatological diseases, rare transplant-related disorders
Research Papers
961 drug discovery papers about Polymyositis, with 2 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
961 drug discovery papers about Polymyositis, with 2 first-in-class and 7 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-19 | JAK inhibitors in areas outside of inflammatory arthritis: focus on connective tissue diseases.
Janus kinase (JAK) inhibitors have emerged as a transformative therapeutic class across autoimmune diseases by targeting multiple cytokine networks implicated in inflammation and fibrosis. Beyond inflammatory arthritis, increasing evidence supports their potential efficacy in connective tissue diseases such as idiopathic inflammatory myopathies, systemic sclerosis, primary Sjögren's disease, and systemic lupus erythematosus. Through modulation of type I/II interferon and interleukin signalling, JAK inhibition exerts broad anti-inflammatory and antifibrotic effects, translating into clinical improvements in cutaneous, articular and pulmonary domains. Early clinical trials and real-world data confirm meaningful responses in refractory disease, though randomized evidence remains limited. Overall, JAK inhibitors represent a promising, mechanistically grounded option for systemic autoimmune diseases, with ongoing studies expected to refine selectivity, indications and long-term safety profiles.
2026-06-08 | Aggressive Nutrition Therapy in a Rehabilitation Hospital for Severe Tachypnoea and Profound Weight Loss With Interstitial Lung Disease: A Case Report.
A 67-year-old male suffering from polymyositis-associated interstitial lung disease (ILD) was transferred to a rehabilitation hospital. Upon admission, the patient presented with severe malnutrition (weight of 32.0 kg; BMI of 12.10 kg/m2; skeletal muscle index of 3.8 kg/m2) and rapid shallow breathing with pronounced exercise-induced tachypnoea. The patient underwent physiotherapy, which included belt electrode skeletal muscle electrical stimulation and progressively titrated aerobic/resistance training. Following the initial stepwise optimisation for transient poor intake, an aggressive nutrition therapy was started. At discharge, the patient gained 4.6 kg in weight, with an increase in skeletal muscle mass from 13.9 to 15.5 kg. The skeletal muscle index had increased to 4.4 kg/m2, representing an increase of 0.6 kg/m2. Furthermore, the duration of continuous aerobic exercise had increased to 30 min, representing a 27-min increase. This case may present a pragmatic strategy for the implementation of aggressive nutrition therapy during rehabilitation for tachypnoeic ILD.
2026-05-27 | Idiopathic Inflammatory Myopathies-Treatment Perspective of Highly Specialised Rheumatology Centre.
Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m2. The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research.
2026-05-08 | Nerandomilast alleviates myositis-associated interstitial lung disease by modulating the non-Smad signalling pathway and activating the cAMP-PKA-RhoA pathway.
Nerandomilast, a selective phosphodiesterase 4B (PDE4B) inhibitor, has been extensively investigated for the treatment of pulmonary fibrosis; however, its therapeutic potential and mechanisms of action in idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) remain to be elucidated. A myositis-associated ILD mouse model was treated with nerandomilast (BI 1015550), and lung pathology was assessed histologically. Human lung microvascular endothelial cells-5a were stimulated with neutrophil extracellular traps (NETs) to induce endothelial-mesenchymal transition (EndMT). Western blotting, immunofluorescence, qPCR and ELISA were employed to analyse pathways and cytokines. PDE4B was upregulated in the lungs of patients with IIM-ILD and in mice. Treatment with BI 1015550 significantly reduced lung inflammation and fibrosis scores, decreased inflammatory cytokines in bronchoalveolar lavage fluid and serum, alleviated muscle inflammation and lowered kinase activity without evident hepatorenal toxicity. Immunofluorescence and immunohistochemistry revealed diminished NET markers, reduced inflammatory cell infiltration (CD3, CD11b, F4/80), suppression of EndMT, downregulation of Ras homolog family member A (RhoA) and inhibition of key fibrotic pathways: phosphorylated phosphoinositide 3-kinase (P-PI3K), phosphorylated protein kinase B (P-AKT), phosphorylated p38 mitogen-activated protein kinase (P-P38), phosphorylated extracellular signal-regulated kinase (P-ERK), phosphorylated nuclear factor kappa-B (P-NF-κB). In vitro, BI 1015550 inhibited phorbol 12-myristate 13-acetate-induced neutrophil extracellular trap formation (NETosis) and EndMT. Nerandomilast alleviates IIM-ILD by inhibiting NET formation and suppressing EndMT in lung microvascular endothelial cells, potentially through non-Smad signalling pathway modulation and cAMP-PKA-RhoA pathway activation. These findings suggest that the specific inhibition of PDE4B is a potential therapeutic approach for IIM-ILD.
2026-02-04 | [Expression of the melanoma 2-mediated pyroptosis pathway in peripheral blood mononuclear cells of patients with idiopathic inflammatory myopathies].
To detect the expression levels of absence in melanoma 2 (AIM2), cysteine aspartate-specific protease-1 (caspase-1), and gasdermin D (GSDMD) in peripheral blood mononuclear cell (PBMC) of patients with idiopathic inflammatory myopathy (IIM) and to explore their role in the pathogenesis of IIM. A total of 30 IIM patients (IIM group) who visited the Department of Rheumatology and Immunology, General Hospital of Northern Theater Command from May 2020 to June 2022 were recruited. Concurrently, 30 healthy volunteers matched by gender and age were recruited from the hospital's Health Examination Center. Clinical information, biochemical and immunological mar-kers, and venous blood samples were collected from the study subjects. Serum double-stranded DNA (dsDNA) levels were detected by fluorescence quantitative method, and the mRNA expression levels of AIM2, caspase-1, GSDMD, interleukin 1β (IL-1β), and IL-18 in PBMC were detected by reverse transcription quantitative real-time PCR (RT-qPCR). The protein expression levels of AIM2, caspase-1, GSDMD, IL-1β, and IL-18 in PBMC were detected using the Western blot (WB) method, and the serum levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA). The IIM group included 10 cases of dermatomyositis (DM), 5 cases of polymyositis (PM), 11 cases of overlap syndrome (OM), and 4 cases of immune-mediated necrotizing myopathy (IMNM). Compared with the healthy control group, the serum levels of dsDNA, IL-1β, and IL-18 were significantly increased in the IIM group and its subgroups (P < 0.05). Except for the fact that there was no statistically significant difference in AIM2 mRNA levels in PBMC of the IMNM subgroup compared to the healthy control group, the expression of AIM2, caspase-1, and GSDMD mRNA was significantly increased in the IIM group and other subgroups (P < 0.05); Except for the comparison of IL-1β mRNA levels in PBMC of the IMNM and OM subgroups with the healthy control group showing no statistical difference, the expression of IL-1β and IL-18 mRNA was significantly increased in the IIM group and other subgroups (P < 0.05); Comparisons between subgroups indicated that the expression of IL-1β mRNA in the DM subgroup was significantly higher than that in the OM and IMNM subgroups, and the expression of IL-18 mRNA in the PM subgroup was significantly higher than that in the DM and OM subgroups (P < 0.05). The expression levels of AIM2, caspase-1, GSDMD, IL-1β, and IL-18 proteins in PBMC of the IIM group and its subgroups were significantly higher than those in the healthy control group (P < 0.05); Comparisons among subgroups revealed that the expression of IL-18 protein in the OM subgroup was significantly higher than that in the PM subgroup (P < 0.05). In the IIM group, the mRNA of caspase-1, GSDMD, and IL-18 showed a positive correlation with AIM2 mRNA, and the protein expression of caspase-1, GSDMD, IL-1β, and IL-18 also showed a positive correlation with AIM2 protein expression. The AIM2 inflammasome-mediated pyroptosis pathway may be involved in the pathogenesis of IIM, providing a theoretical basis for further research on the etiology of IIM and the development of new therapies.
cell therapies
2026-07-13 | POLYMYOSITIS ASSOCIATED WITH PRIMARY BILIARY CIRRHOSIS AND OVARIAN CARCINOMA – CLINICAL CASE PRESENTATION AND LITERATURE REVIEW
Polymyositis is an idiopathic inflammatory myopathy classified under a heterogeneous group of autoimmune diseases predominantly presenting with symmetrical proximal muscle weakness, weakness of neck muscles with the manifestation of a "dropped head" symptom, dysphagia, dysphonia; elevated serum levels of creatine kinase (CK), sometimes in conjunction with elevated liver enzymes; characteristic EMG findings and muscle biopsy. The presence of myositis-specific antibodies in more than half of the patients facilitates the definition of distinct clinical subtypes and aids in accurate diagnosis, with an associated higher risk of involvement of other organs and systems such as the lungs, heart, liver, etc., most commonly presenting as interstitial pulmonary fibrosis, cardiomyopathy, and significantly less frequently primary biliary cirrhosis. A twofold increase in malignancies has been established compared to the general population, or the manifestation of myositis can be presented as a paraneoplastic syndrome. The first-line treatment method is the administration of intravenous corticosteroids in moderate or high doses combined with cytostatic therapy, with rare necessity for intravenous immunoglobulin administration, while plasmapheresis is considered an inapplicable method. We report a case of polymyositis with characteristic clinical and serological findings, with severe respiratory failure, developing twice in the absence of interstitial pulmonary fibrosis, primarily secondary myocardial damage during disease activity, and the presence of asymptomatic ovarian cancer and primary biliary cirrhosis discovered during the course of the disease, demonstrating the best therapeutic effectiveness from plasmapheresis. Accurate diagnosis relies on clinical, electrophysiological, and immunological findings, posing diagnostic challenges and questions that require the collaborative efforts of a multidisciplinary team.
2026-05-19 | Chimeric antigen receptor T-cell (CAR-T) therapy and other cellular immunotherapy treatments for idiopathic inflammatory myopathies.
Idiopathic inflammatory myopathies (IIM), including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), anti-synthetase syndrome (ASyS), overlap myositis and polymyositis, are heterogeneous autoimmune diseases characterized by immune-mediated skeletal muscle injury and frequent extra-muscular organ involvement. Despite recent therapeutic advances, many IIM patients have persistent disease activity, medication toxicity, or steroid dependence with current treatments. Increasing evidence implicates autoreactive B cells and autoantibody-producing plasma cells as central drivers of disease activity in several IIM subtypes, providing a strong rationale for B-cell- targeted therapies. While monoclonal antibody-based B-cell depletion strategies such as rituximab have demonstrated variable efficacy, their inability to effect persistent, intense depletion of tissue autoreactive B-cell populations often limit their success. Chimeric antigen receptor T-cell (CAR-T) and related cellular immunotherapies were originally developed against hematologic malignancies, but have recently emerged potentially transformative therapeutic options for autoimmune diseases. CAR-T cells targeting CD19 and other B-cell antigens have demonstrated the capacity to induce deep and durable B-cell depletion, and may even lead to "immune reset" with long-lived autoimmunity remission in diseases such as systemic lupus erythematosus and systemic sclerosis. Early clinical experiences now suggest that CAR-T therapy may offer similar promise in refractory IIM, particularly in phenotypes that include pathogenic autoantibodies, such as ASyS, DM, IMNM. This review provides a synopsis of current knowledge on the immunopathogenesis of IIM relevant to CAR-T and other cellular immunotherapy, outlines CAR-T technology and the mechanistic rationale for its use in IIM, and critically appraises emerging clinical CAR-T treatment data in IIM. We also discuss safety considerations, practical challenges, and future directions, with a focus on how CAR-based immunotherapies may reshape treatment paradigms for refractory inflammatory myopathies.
2026-05-18 | Case Report: Sustained immune and pulmonary recovery three years after hematopoietic stem cell transplantation for ITCH E3 ubiquitin ligase deficiency.
Itchy E3 ubiquitin ligase deficiency (ITCH deficiency) is a rare monogenic immune dysregulation syndrome characterized by early-onset multisystem autoimmunity and significant morbidity and mortality. Only one prior case report has described a patient treated with hematopoietic stem cell transplantation (HSCT) with clinical improvement, and no established disease-modifying or curative therapy algorithm exists. We describe a female patient who presented in early childhood with chronic lung disease requiring tracheostomy and long-term mechanical ventilation and later developed progressive muscle weakness. She was diagnosed with steroid-responsive juvenile polymyositis and subsequently accumulated multiple autoimmune manifestations including autoimmune hepatitis, enteropathy, psoriasis, inflammatory arthritis, and Sjögren's-like parotitis. Genetic testing ultimately identified compound heterozygous pathogenic variants in ITCH. Despite prolonged treatment with multiple immunosuppressive and biologic therapies, she remained prednisone dependent with poor disease control and substantial treatment-related morbidity. At 20 years of age, she underwent allogeneic hematopoietic stem cell transplantation. Following transplantation, she achieved sustained resolution of autoimmune disease activity, was successfully weaned from all immunosuppressive therapy, and was decannulated from chronic mechanical ventilation, with marked improvement in functional status and quality of life. This is the second reported case demonstrating the benefit of hematopoietic stem cell transplant (HSCT) in ITCH deficiency and provides evidence of durable multisystem clinical remission and recovery of long-standing pulmonary and musculoskeletal disease. These findings support consideration of HSCT as a therapeutic option in carefully selected patients with severe, refractory autoimmune manifestations due to ITCH deficiency and raise the possibility that earlier consideration in the disease course may mitigate cumulative disease- and treatment-related morbidity.
2025-05-12 | Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases.
Rheumatic diseases are chronic immune-mediated disorders affecting multiple organ systems and significantly impairing patients' quality of life. Current treatments primarily provide symptomatic relief without offering a cure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their ability to differentiate into various cell types and their immunomodulatory, anti-inflammatory, and regenerative properties. This review aims to summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions. A comprehensive review of preclinical and clinical studies on MSC therapy in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis, Sjögren's syndrome, Crohn's disease, fibromyalgia, systemic sclerosis, dermatomyositis, and polymyositis, was conducted. Emerging strategies to enhance MSC efficacy and overcome current limitations were also analyzed. Evidence from preclinical and clinical studies suggests that MSC therapy can reduce inflammation, modulate immune responses, and promote tissue repair in various rheumatic diseases. Clinical trials have demonstrated potential benefits, including symptom relief and disease progression delay. However, challenges such as variability in treatment response, optimal cell source and dosing, long-term safety concerns, and regulatory hurdles remain significant barriers to clinical translation. Standardized protocols and further research are required to optimize MSC application. MSC therapy holds promise for managing rheumatic diseases, offering potential disease-modifying effects beyond conventional treatments. However, large-scale, well-controlled clinical trials are essential to establish efficacy, safety, and long-term therapeutic potential. Addressing current limitations through optimized treatment protocols and regulatory frameworks will be key to its successful integration into clinical practice.
2025-03-24 | Carbamoyl phosphate synthetase 1 deficiency manifested in an adult treated with prednisone for polymyositis, and cured by live-donor liver transplantation.
Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM#237300) is a rare inherited disorder due to complete or partial lack of the CPS1 enzyme. Polymyositis is a relatively rare systemic inflammatory autoimmune disease. Here, we report a 59-year-old Japanese woman diagnosed with late-onset CPS1 deficiency during polymyositis treatment. The polymyositis appeared two years before the diagnosis of CPS1 deficiency. Prednisolone (PSL) at 35 mg/day initial dosage, promptly alleviated the symptoms. However, the patient, without apparent cause, suddenly developed confusion progressing to unconsciousness and coma. Upon admission, the patient's plasma ammonia levels were 458 μg/dL (269 μM). Plasma amino acid analysis revealed decreased citrulline levels and elevated glutamine levels. Genetic analysis of CPS1 (OMIM *608307) showed homozygosity for the likely pathogenic variant c.2397G > A (p.Met799Ile), leading to the diagnosis of CPS1 deficiency. The patient responded to pharmacotherapy and continuous hemodialysis. However, the patient experienced hyperammonemia decompensation events while on pharmacotherapy at home, which were successfully managed with emergency treatment and/or hemodialysis. Subsequently, after liver transplantation, the patient's plasma ammonia levels consistently remained at normal. This case illustrates late-onset CPS1 deficiency manifested in an adult treated with PSL for polymyositis, and the cure of its enzyme deficiency by live-donor liver transplantation.
proteins
2026-06-25 | Acthar Gel treatment in patients with rheumatoid arthritis, systemic lupus erythematosus, or dermatomyositis/polymyositis: analysis of physician-reported charts.
Aim: To examine the characteristics, treatment patterns, and physicians' assessments of outcomes for patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or dermatomyositis/polymyositis (DM/PM) who received Acthar Gel. Materials & methods: This survey-based medical chart review study asked rheumatologists who met specific inclusion criteria to abstract data from patient records covering the period from April 2022 to November 2024. Eligible patients were adults ≥18 years diagnosed with RA, SLE, or DM/PM, treated with Acthar Gel for ≤24 months. An online questionnaire screened and identified contributing physicians and collected anonymized patient data (baseline demographic, medical history, concomitant medications, Acthar Gel treatment history, and physicians' assessment of health status, symptom severity, treatment outcomes with Acthar Gel). Results: The study population comprised 73 patients with RA (average age 50 years; 49 [67%] female; 44 [60%] White/non-Hispanic), 56 with SLE (average age 42 years; 47 [84%] female; 28 [50%] African-American), and 104 with DM/PM (average age 52 years; 69 [66%] female; 62 [60%] White/non-Hispanic). Patients had received Acthar Gel for an average of 9 (RA) or 8 months (SLE, DM/PM), with most receiving treatment at the time of the study. Per physicians' assessment, health status improved in 68 (93%) patients with RA, 50 (89%) patients with SLE, and 100 (96%) patients with DM/PM after starting treatment with Acthar Gel. The most common treatment goals achieved in patients with improved overall health status were improved overall symptoms, pain, physical function, and corticosteroid use in the RA cohort; overall symptoms, pain, corticosteroid use, and fatigue in the SLE cohort; and overall symptoms, strength, physical function, and corticosteroid use in the DM/PM cohort. Conclusion: These findings support the use of Acthar Gel as a potential treatment option for appropriate patients with RA, SLE, or DM/PM.
2026-03-26 | Interleukin-2 Deprived State of Regulatory T cells and Their Recovery by Low-Dose Interleukin-2 in Patients With Inflammatory Myopathies.
Regeneration and expansion of Treg by low-dose interleukin-2 (IL-2) therapy is considered a potential treatment strategy for a wide range of autoimmune diseases. To provide a pathophysiologically-based rationale for low-dose IL-2 therapy, we investigated whether reversible defects in the Treg-IL-2 axis emerge in inflammatory myopathies. CD4+ T cell subsets from patients with polymyositis (PM) or dermatomyositis (DM) (n = 20) and healthy controls (HC) (n = 19) and peripheral blood mononuclear cells (PBMC) from eight patients that were stimulated in vitro for 24 hours with different concentrations of recombinant human IL-2 were analyzed by multicolor flow cytometry. Messenger RNA (mRNA) expressions of IL2RA, IL2RB, IL2RB, ENTPD1, IKZF2, and CTLA4 were quantified by real-time polymerase chain reaction in IL-2 stimulated PBMC (n = 6). Two patients with refractory PM/DM were treated with low-dose IL-2 therapy for eight weeks and monitored for clinical responses and changes in Treg subsets. Frequencies of Treg expressing CD25 at high levels (CD25hi Treg) and of CXCR5+ Treg were reduced in patients with PM/DM compared with HC (P = 0.0052; P = 0.0661), particularly in active myositis (P = 0.0036; P = 0.0335). Stimulation with low doses of IL-2 selectively enhanced expression of CD25 molecules by Treg, leading to an increase in the CD25hi Treg subset (P < 0.05) and augmented mRNA expression of several immunoregulatory molecules (P < 0.05). Low-dose IL-2 therapy induced decreases in muscle enzymes that were accompanied by a sustained expansion of CD25+ Treg. Our data suggest that shortage of IL-2 is pathophysiologically relevant in PM/DM. Recovery and expansion of Treg by low-dose IL-2 therapy could thus be a promising targeted treatment option.
2026-02-13 | [Macrophage activation syndrome in a young patient with polymyositis].
Haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) is a life-threatening condition characterised by systemic hyperinflammation and is often triggered by infections, malignancies, or autoimmune disease. The HScore is a diagnostic tool used to estimate the likelihood of HLH/MAS based on clinical, biochemical, and histological findings. This case describes a patient with polymyositis developing MAS, indicated by an HScore of 219. He was treated with IV anakinra, steroids, and immunoglobulin, leading to significant improvement. This case emphasises the importance of early MAS recognition and timely intervention in critical conditions.
2024-03-25 | Pathogenicity of functionally activated PD-1+CD8+ cells and counterattacks by muscular PD-L1 through IFNγ in myositis.
Programmed-cell-death 1 (PD-1) expression is associated not only with T-cell activation but with exhaustion. Specifically, PD-1+ T cells present an exhausted phenotype in conditions of chronic antigen exposure, such as tumor microenvironments and chronic viral infection. However, the immune status regarding exhaustion of PD-1+CD8+ T cells in chronic autoimmune diseases including idiopathic inflammatory myopathies (IIMs) remains unclear. We aimed to clarify the role of PD-1+CD8+ T cells and PD-1 ligand (PD-L1) in IIMs. We showed that PD-1+ cells infiltrated into PD-L1-expressing muscles in patients with IIMs and immune checkpoint inhibitor-related myopathy. According to the peripheral blood immunophenotyping, the PD-1+CD8+ cell proportions were comparable between the active and inactive patients. Of note, PD-1+CD8+ cells in the active patients highly expressed cytolytic molecules, indicating their activation, while PD-1-CD8+ cells expressed low levels of cytolytic molecules in the active and inactive patients. A part of PD-1+CD8+ cells expressed the HMG-box transcription factor TOX highly and presented the exhausted phenotype in the active patients. Among PD-1+CD4+ T cells, PD-1highCXCR5-CD45RO+CD4+ peripheral helper T cells were increased in the active patients. PD-L1-deficient mice developed severer C-protein-induced myositis (CIM), a model of polymyositis, with abundant infiltration of PD-1+CD8+ cells expressing cytolytic molecules than wild-type mice, indicating pathogenicity of the PD-1+CD8+ cells and the protective role of PD-L1. The deficiency of IFNγ, a general PD-L1-inducer, impaired muscular PD-L1 expression and exacerbated CIM, indicating IFNγ-dependent muscular PD-L1 regulation. IFNγ-induced PD-L1 on myotubes was protective in an established muscle injury model. In conclusion, PD-1+CD8+ T cells rather than PD-1-CD8+ T cells were a pathogenic subset of IIMs. Muscular PD-L1 was regulated by IFNγ and exerted protective properties in IIMs.
2023-12-28 | Polymyositis following varicella and mumps infection in adults: report of two cases.
Idiopathic immune myopathies (IIMs) are autoimmune diseases caused by immune-mediated muscle damage. The etiology remains unclear. Epidemiological and experimental studies, both in animals and humans, hint at viruses as major environmental factors able to trigger aberrant immune responses through many different mechanisms. However, only a few cases of either dermatomyositis or polymyositis following a specific viral infection have been reported in the literature. The objective of this study is to describe the clinical features and the treatment strategy of 2 cases of polymyositis developing shortly after chickenpox and mumps, respectively, and to review the existing literature on the topic. The clinical records of the 2 patients suspected to have developed inflammatory myositis following a viral infection were reviewed. Their clinical history, main laboratory findings, and treatment outcome are presented here. Moreover, a literature search was performed in the PubMed and MEDLINE databases to identify reports describing the association between viral infections and IIMs in patients aged ≥18. The 2 patients reported here developed polymyositis shortly after chickenpox and mumps, respectively, suggesting a causal role for viruses in triggering autoimmunity. Only a few reports published between 1990 and 2020 were found in the literature, possibly linking infections to myositis development. Intravenous immunoglobulin and rituximab were effective for the treatment of viral-triggered polymyositis.
antibodies
2026-08-10 | Outcomes of Immune Check Point Inhibitor Use in US Veterans With Pre-Existing Idiopathic Inflammatory Myopathies: Case Series and Literature Review.
Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre-existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision-making and close monitoring.
2026-08-08 | Pulmonary arterial hypertension in polymyositis: a case report
Pulmonary arterial hypertension (PAH) associated with connective tissue diseases is a lifethreatening condition in which elevated pressure in the pulmonary vasculature leads to a marked increase in right heart afterload, causing severe right ventricular failure and premature death. PAH is most frequently associated with systemic sclerosis and systemic lupus erythematosus. Polymyositis is a rare autoimmune disease resulting from aberrant activation of cytotoxic Tlymphocytes and macrophages against autologous muscle tissue, leading to inflammatory myopathy. In polymyositis, the inflammatory process may involve the vascular bed (small pulmonary artery vasculitis), which can lead to PAH. PAH in polymyositis is an extremely rare entity. This article presents a clinical observation of a patient with idiopathic polymyositis who developed a fatal complication — PAH — over several years. Key diagnostic aspects, clinical course features, and characteristic signs of the disease are demonstrated. The need for a multidisciplinary approach in managing patients with this condition is emphasised, and the importance of accumulating data on pulmonary hypertension in polymyositis is highlighted
2026-08-08 | A systematic review of abatacept and belatacept in immune-mediated diseases.
Abatacept (ABA) and belatacept (BEL) are immunomodulatory fusion proteins in which the extracellular domain of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is linked to the Fc fragment of human IgG1. Functionally, they bind to cell surface antigens CD80 and CD86 on antigen-presenting cells, thereby preventing CD28-mediated costimulatory signaling. This systematic review aims to evaluate the clinical efficacy of ABA and BEL in immune-mediated diseases, focusing on indications currently not approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). We searched PubMed and Web of Science for reports describing clinical efficacy of ABA or BEL in at least one patient with immune-mediated conditions outside FDA/EMA-approved indications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided our data reporting. Of 5333 articles initially extracted, 2778 unique records were screened after de-duplication, and 96 matched our criteria and were included in this study. ABA was beneficial in patients diagnosed with Sjögren's syndrome (particularly secondary forms); autoimmunity in association with immunodeficiency; early, inflammatory and normal-like subtypes of systemic sclerosis; scleroderma; arthritis in systemic lupus erythematosus; inflammatory myopathies (polymyositis, immune-mediated necrotizing myositis, and antisynthetase syndrome); and giant-cell arteritis. Lower-level evidence studies reported positive results using ABA to treat granulomatosis with polyangiitis; relapsing polychondritis; sarcoidosis; and inflammatory eye diseases. Results of several studies highlighted the positive impact of ABA on arthritis in patients taking this drug for other indications. Likewise, several autoimmune diseases responded effectively to ABA when used to treat concomitant rheumatoid arthritis. Positive serological responses suggesting downstream modulation of B cell activation were reported in several randomized controlled trials. BEL was used after kidney transplantation in patients with proteinuric kidney disease or lupus nephritis, and in a few non-transplanted CTLA-4 haploinsufficiency carriers for immunodeficiency-associated autoimmunity. Our results provide a comprehensive summary of the efficacy of ABA and BEL across a broad spectrum of autoimmune diseases.
2026-08-06 | A Case Report on Polymyositis
Polymyositis is a chronic autoimmune inflammatory myopathy marked by symmetrical proximal muscle weakness due to immune-mediated muscle fiber damage.The disease predominantly affects adults, exhibiting a higher incidence in females, and is characterized by immune activation involving cytotoxic T lymphocytes and inflammatory mediators.Polymyositis symptoms include trouble getting up from a chair, climbing stairs, or lifting things. These symptoms are often accompanied by fatigue, muscle pain, trouble swallowing (dysphagia), and possible breathing problems. Patients exhibit progressive muscle weakness, dysphagia, and systemic manifestations which can severely affect quality of life.Diagnosis entails clinical assessment, laboratory analyses including elevated creatine kinase levels, autoantibody testing, imaging modalities, electromyography, and muscle biopsy for validation. The main goal of management is to make muscles stronger and improve functional outcomes through drug treatments. Corticosteroids are the first-line treatment, and immunosuppressive drugs like methotrexate and azathioprine are also used. .To improve the prognosis and the quality of life for patients, it is important to diagnose them early and use a multidisciplinary approach to treatment.
2026-07-08 | The onset of systemic scleroderma in combination with polymyositis (cross-form) after suffering from COVID-19
According to current concepts, immuno-inflammatory rheumatic diseases are similar to COVID-19 in terms of clinical manifestations, immune responses and pathogenetic mechanisms, which is due to the systemic nature of the lesion. In patients with genetic prerequisites, both infection and vaccination against COVID-19 can trigger the immune-inflammatory process. The article presents a clinical observation demonstrating the diagnostic difficulties encountered in the diagnosis of systemic scleroderma and polymyositis that developed after COVID-19. Оnly timely diagnosis and adequate therapy can significantly improve the condition and, consequently, the prognosis of this category of patients. A special feature of this case is the absence of autoimmune markers – immunoblots confirming the diagnosis of systemic scleroderma and polymyositis in the presence of vivid clinical symptoms of each of these diseases. The addition of rituximab to the standard basic therapy increases its effectiveness.
other
2022-03-30 | MicroRNA-409-3p regulates macrophage migration in polymyositis through targeting CXCR4.
Macrophage migration and infiltration contribute to the pathogenesis of polymyositis (PM). This study aims to investigate the effect and underlying mechanism of miR-409-3p on macrophage migration in PM. The GSE143845 database was used to predict the altered expression of microRNAs (miRNAs) in PM. The quantitative real-time PCR (qRT-PCR), western blot and Transwell assay were performed to detect migration of macrophages and expressions of related molecules. A luciferase activity assay was conducted to confirm the binding of miR-409-3p and CXCR4 3'-UTR. Next, a mouse model of experimental autoimmune myositis (EAM) was established. Haematoxylin and eosin (HE) staining, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to measure associated factors. MiR-409-3p was downregulated in PM of GSE143845 database and patients. Differently, the serum creatine kinase (s-CK), TNF-α, and IL-6 in patients with PM were increased. Furthermore, miR-409-3p mimic transfection reduced the migration of macrophages and CXCR4 levels, while miR-409-3p inhibitor exerted the opposite effects. CXCR4 was a target of miR-409-3p, and the effect of CXCR4 on promoting macrophage migration was reversed by miR-409-3p mimic. In vivo, miR-409-3p agomir injection reduced inflammatory cells, macrophages, and TNFα and IL-6 levels in muscles and serum of EAM mouse models. In conclusion, miR-409-3p reduces the migration of macrophages through negatively regulating CXCR4 expression in PM.
2020-05-31 | Muscle Weakness in Myositis: MicroRNA‐Mediated Dystrophin Reduction in a Myositis Mouse Model and Human Muscle Biopsies
Objective Muscle inflammation is a feature in myositis and Duchenne muscular dystrophy ( DMD ). Autoimmune mechanisms are thought to contribute to muscle weakness in patients with myositis. However, a lack of correlation between the extent of inflammatory cell infiltration and muscle weakness indicates that nonimmune pathologic mechanisms may play a role. The present study focused on 2 micro RNA (mi RNA ) sets previously identified as being elevated in the muscle of patients with DMD —an “inflammatory” mi RNA set that is dampened with glucocorticoids, and a “dystrophin‐targeting” mi RNA set that inhibits dystrophin translation—to test the hypothesis that these mi RNA s are similarly dysregulated in the muscle of patients with myositis, and could contribute to muscle weakness and disease severity. Methods A major histocompatibility complex class I–transgenic mouse model of myositis was utilized to study gene and mi RNA expression and histologic features in the muscle tissue, with the findings validated in human muscle biopsy tissue from 6 patients with myositis. Mice were classified as having mild or severe myositis based on transgene expression, body weight, histologic disease severity, and muscle strength/weakness. Results In mice with severe myositis, muscle tissue showed mononuclear cell infiltration along with elevated expression of type I interferon and NF ‐κB–regulated genes, including Tlr7 (3.8‐fold increase, P < 0.05). Furthermore, mice with severe myositis showed elevated expression of inflammatory mi RNA s (miR‐146a, miR‐142‐3p, miR‐142‐5p, miR‐455‐3p, and miR‐455‐5p; ~3–40‐fold increase, P < 0.05) and dystrophin‐targeting mi RNA s (miR‐146a, miR‐146b, miR‐31, and miR‐223; ~3–38‐fold increase, P < 0.05). Bioinformatics analyses of chromatin immunoprecipitation sequencing (ChIP‐seq) data identified at least one NF ‐κB consensus element within the promoter/enhancer regions of these mi RNA s. Western blotting and immunofluorescence analyses of the muscle tissue from mice with severe myositis demonstrated reduced levels of dystrophin. In addition, elevated levels of NF ‐κB–regulated genes, TLR 7 , and mi RNA s along with reduced dystrophin levels were observed in muscle biopsy tissue from patients with histologically severe myositis. Conclusion These data demonstrate that an acquired dystrophin deficiency may occur through NF ‐κB–regulated mi RNA s in myositis, thereby suggesting a unifying theme in which muscle injury, inflammation, and weakness are perpetuated both in myositis and in DMD .
2020-02-21 | Reduced miR-146a Promotes REG3A Expression and Macrophage Migration in Polymyositis and Dermatomyositis
Background: Growing evidence from studies elsewhere have illustrated that microRNAs (miRNAs) play important roles in Polymyositis and Dermatomyositis (PM/DM). However, little has been reported on their relationship with regenerating islet-derived protein 3-alpha (REG3A) as well as their associative roles in macrophage migration. Therefore, this study sought to establish the association between miR-146a and REG3A as well as investigate their functional roles in macrophage migration and PM/DM pathogenesis. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from PM/DM patients and healthy controls through density centrifugation. Macrophages were obtained from monocytes purified from PBMCs via differentiation prior to their transfection with microRNA (miRNA) or plasmids to investigate cell migration with transwell assay. An experimental autoimmune myositis (EAM) murine model was used to investigate PM/DM. Real-time PCR and western blot analysis were conducted to determine the expression levels of miR-146a, IFN-γ, IL-17A and REG3A. Results: The mRNA expression level of miR-146a markedly decreased while the mRNA level of REG3A, IFN-γ and IL-17A expression increased substantially in PBMCs from PM/DM patients compared with the healthy controls. The levels of IFN-γ and IL-17A in serum from PM/DM patients was much higher than the healthy controls. Immunohitochemistry analysis showed that REG3A expression increased in muscle tissues from patients. Consistent with clinical data, the mRNA expression level of miR-146a also decreased whereas the mRNA and protein level of REG3A, IFN-γ and IL-17A significantly increased in the muscle tissues of EAM mice. Moreover, miR-146a inhibited monocyte-derived macrophage migration and REG3A promoted macrophage migration. In addition, IL-17A induced REG3A expression, while miR146a inhibited expression of REG3A in monocyte-derived macrophages from the PBMCs of the healthy donors. Notably, inhibition of macrophage migration by miR-146a was via the reduction of REG3A expression. Conclusions: Reduced miR-146a expression in PM/DM leads to increased REG3A expression that increases inflammatory macrophage migration, which may be a possible underlying mechanism of DM/PM pathogenesis.
2018-06-29 | MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1
The downregulation of microRNA (miR)-381 has been detected in various diseases. The present study aimed to investigate the effects, and underlying mechanisms of miR-381 on inflammation and macrophage infiltration in polymyositis (PM). A mouse model of experimental autoimmune myositis (EAM) was generated in this study. Hematoxylin and eosin staining was conducted to detect the inflammation of muscle tissues. In addition, ELISA and immunohistochemistry were performed to determine the expression levels of associated factors, and reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression levels of related mRNAs and proteins. A luciferase activity assay was used to confirm the binding of miR-381 and high mobility group box 1 (HMGB1) 3' untranslated region. Transwell assays were also performed to assess the migratory ability of macrophages. The results demonstrated that serum creatine kinase (s-CK), HMGB1 and cluster of differentiation (CD)163 expression in patients with PM were increased compared within healthy controls. Conversely, the expression levels of miR-381 were downregulated in patients with PM. Furthermore, high HMGB1 expression was associated with poor survival rate in patients with PM. In the mouse studies, muscle inflammation and CD163 expression were decreased in the anti-IL-17 and anti-HMGB1 groups, compared with in the EAM model group. The expression levels of s-CK, HMGB1, IL-17 and intercellular adhesion molecule (ICAM)-1 were also downregulated in response to anti-IL-17 and anti-HMGB1. These findings indicated that HMGB1 was closely associated with inflammatory responses. In addition, the present study indicated that transfection of macrophages with miR-381 mimics reduced the migration of inflammatory macrophages, and the expression levels of HMGB1, IL-17 and ICAM-1. Conversely, miR-381 inhibition exerted the opposite effects. The effects of miR-381 inhibitors were reversed by HMGB1 small interfering RNA. In conclusion, miR-381 may reduce inflammation and the infiltration of macrophages; these effects were closely associated with the downregulation of HMGB1.
2017-02-13 | MiR-146a Regulates Inflammatory Infiltration by Macrophages in Polymyositis/Dermatomyositis by Targeting TRAF6 and Affecting IL-17/ICAM-1 Pathway.
The primary objective of this study was to investigate the role of miR-146a in inducing the inflammatory infiltration of macrophages in polymyositis/dermatomyositis (PM/DM) through targeting TNF receptor associated factor 6 (TRAF6), which may further down-regulate the Interleukin-17 (IL-17)/Intercellular Adhesion Molecule 1 (ICAM-1) pathway. Biopsies were collected from PM/DM patients and healthy volunteers. PM/DM model establishment and macrophage isolation were performed on Sprague Dawley (SD) rats. Model rats and macrophages were treated with anti-IL-17, anti-ICAM-1, miR-146a mimics, miR-146a inhibitors, and TRAF6 siRNAs. Serum creatine phosphokinase (S-CK) expression was assessed using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry assay was performed to analyze CD163 expression in muscle samples. Furthermore, we used transwell assay to test cell migration; RT-PCR and western blot were carried out to determine the expression of miR-146a, TRAF6, IL-17, and ICAM-1. The S-CK, TRAF6, IL-17 and ICAM-1 levels were higher in PM/DM patients compared with healthy controls and were down-regulated after the conventional treatment. Treatment with miR-146a mimics, anti-IL-17 and anti-ICAM-1 decreased the expression of IL-17 and ICAM-1, whereas miR-146a inhibitors exerted the opposite effects. The effects of miR-146a inhibitors were suppressed by treatment with TRAF6 siRNA. In addition, the luciferase reporter assay validated the targeting relationship between miR-146a and TRAF6. MiR-146a regulates inflammatory macrophage infiltration in PM/DM by targeting TRAF6 and affecting the IL-17/ICAM-1 pathway.
small molecules
2026-06-19 | JAK inhibitors in areas outside of inflammatory arthritis: focus on connective tissue diseases.
Janus kinase (JAK) inhibitors have emerged as a transformative therapeutic class across autoimmune diseases by targeting multiple cytokine networks implicated in inflammation and fibrosis. Beyond inflammatory arthritis, increasing evidence supports their potential efficacy in connective tissue diseases such as idiopathic inflammatory myopathies, systemic sclerosis, primary Sjögren's disease, and systemic lupus erythematosus. Through modulation of type I/II interferon and interleukin signalling, JAK inhibition exerts broad anti-inflammatory and antifibrotic effects, translating into clinical improvements in cutaneous, articular and pulmonary domains. Early clinical trials and real-world data confirm meaningful responses in refractory disease, though randomized evidence remains limited. Overall, JAK inhibitors represent a promising, mechanistically grounded option for systemic autoimmune diseases, with ongoing studies expected to refine selectivity, indications and long-term safety profiles.
2026-06-08 | Aggressive Nutrition Therapy in a Rehabilitation Hospital for Severe Tachypnoea and Profound Weight Loss With Interstitial Lung Disease: A Case Report.
A 67-year-old male suffering from polymyositis-associated interstitial lung disease (ILD) was transferred to a rehabilitation hospital. Upon admission, the patient presented with severe malnutrition (weight of 32.0 kg; BMI of 12.10 kg/m2; skeletal muscle index of 3.8 kg/m2) and rapid shallow breathing with pronounced exercise-induced tachypnoea. The patient underwent physiotherapy, which included belt electrode skeletal muscle electrical stimulation and progressively titrated aerobic/resistance training. Following the initial stepwise optimisation for transient poor intake, an aggressive nutrition therapy was started. At discharge, the patient gained 4.6 kg in weight, with an increase in skeletal muscle mass from 13.9 to 15.5 kg. The skeletal muscle index had increased to 4.4 kg/m2, representing an increase of 0.6 kg/m2. Furthermore, the duration of continuous aerobic exercise had increased to 30 min, representing a 27-min increase. This case may present a pragmatic strategy for the implementation of aggressive nutrition therapy during rehabilitation for tachypnoeic ILD.
2026-05-27 | Idiopathic Inflammatory Myopathies-Treatment Perspective of Highly Specialised Rheumatology Centre.
Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are chronic immune-mediated disorders, causing striated muscle weakness and extramuscular symptoms. Real-world, single-centre data are needed to interpret phenotype patterns and evolving therapies. Methods: A single-centre, retrospective cohort study was conducted at the Rheumatology Clinic of the National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland from 1 January 2022 to 31 December 2025. Data included demographics, IIM subtypes, extramuscular involvement, co-existing Sjögren disease (SD), biopsy results, autoantibodies, and treatment. Due to sample size, descriptive analysis was used. Results: The study included 35 patients (31.4% men). Mean age was 50.7 years; mean body mass index (BMI) was 26.0 kg/m2. The cohort consisted of 10 dermatomyositis (DM), one polymyositis (PM), two immune-mediated necrotising myopathy (IMNM), one inclusion body myositis (IBM), 16 anti-synthetase syndrome (ASyS), four juvenile dermatomyositis (JDM), and one clinically amyopathic dermatomyositis (CADM). SD co-occurred in eight cases, including six cases of ASyS. Anti-Jo1 was observed in 13 ASyS cases and one DM. Glucocorticoids (GCSs) were administered in all patients for induction in addition to cyclophosphamide (28.6%), mycophenolate mofetil (MMF) (51.4%), and methotrexate (MTX) (17.1%). Maintenance therapy included MTX (20%), MMF (31.4%), rituximab (34.3%), azathioprine (AZA) (42.9%), and others. Two DM, two JDM, and one ASyS patient received JAK inhibitors, one DM and one JDM anifrolumab, one IBM sirolimus, and four patients with interstitial lung disease (ILD) nintedanib. Conclusions: This Polish single-centre cohort shows effective use of novel therapies for IIM. Sirolimus, JAK inhibitors, and nintedanib were effective. Co-occurrence of SD in ASyS patients requires further research.
2026-05-08 | Nerandomilast alleviates myositis-associated interstitial lung disease by modulating the non-Smad signalling pathway and activating the cAMP-PKA-RhoA pathway.
Nerandomilast, a selective phosphodiesterase 4B (PDE4B) inhibitor, has been extensively investigated for the treatment of pulmonary fibrosis; however, its therapeutic potential and mechanisms of action in idiopathic inflammatory myopathies-associated interstitial lung disease (IIM-ILD) remain to be elucidated. A myositis-associated ILD mouse model was treated with nerandomilast (BI 1015550), and lung pathology was assessed histologically. Human lung microvascular endothelial cells-5a were stimulated with neutrophil extracellular traps (NETs) to induce endothelial-mesenchymal transition (EndMT). Western blotting, immunofluorescence, qPCR and ELISA were employed to analyse pathways and cytokines. PDE4B was upregulated in the lungs of patients with IIM-ILD and in mice. Treatment with BI 1015550 significantly reduced lung inflammation and fibrosis scores, decreased inflammatory cytokines in bronchoalveolar lavage fluid and serum, alleviated muscle inflammation and lowered kinase activity without evident hepatorenal toxicity. Immunofluorescence and immunohistochemistry revealed diminished NET markers, reduced inflammatory cell infiltration (CD3, CD11b, F4/80), suppression of EndMT, downregulation of Ras homolog family member A (RhoA) and inhibition of key fibrotic pathways: phosphorylated phosphoinositide 3-kinase (P-PI3K), phosphorylated protein kinase B (P-AKT), phosphorylated p38 mitogen-activated protein kinase (P-P38), phosphorylated extracellular signal-regulated kinase (P-ERK), phosphorylated nuclear factor kappa-B (P-NF-κB). In vitro, BI 1015550 inhibited phorbol 12-myristate 13-acetate-induced neutrophil extracellular trap formation (NETosis) and EndMT. Nerandomilast alleviates IIM-ILD by inhibiting NET formation and suppressing EndMT in lung microvascular endothelial cells, potentially through non-Smad signalling pathway modulation and cAMP-PKA-RhoA pathway activation. These findings suggest that the specific inhibition of PDE4B is a potential therapeutic approach for IIM-ILD.
2026-02-04 | [Expression of the melanoma 2-mediated pyroptosis pathway in peripheral blood mononuclear cells of patients with idiopathic inflammatory myopathies].
To detect the expression levels of absence in melanoma 2 (AIM2), cysteine aspartate-specific protease-1 (caspase-1), and gasdermin D (GSDMD) in peripheral blood mononuclear cell (PBMC) of patients with idiopathic inflammatory myopathy (IIM) and to explore their role in the pathogenesis of IIM. A total of 30 IIM patients (IIM group) who visited the Department of Rheumatology and Immunology, General Hospital of Northern Theater Command from May 2020 to June 2022 were recruited. Concurrently, 30 healthy volunteers matched by gender and age were recruited from the hospital's Health Examination Center. Clinical information, biochemical and immunological mar-kers, and venous blood samples were collected from the study subjects. Serum double-stranded DNA (dsDNA) levels were detected by fluorescence quantitative method, and the mRNA expression levels of AIM2, caspase-1, GSDMD, interleukin 1β (IL-1β), and IL-18 in PBMC were detected by reverse transcription quantitative real-time PCR (RT-qPCR). The protein expression levels of AIM2, caspase-1, GSDMD, IL-1β, and IL-18 in PBMC were detected using the Western blot (WB) method, and the serum levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA). The IIM group included 10 cases of dermatomyositis (DM), 5 cases of polymyositis (PM), 11 cases of overlap syndrome (OM), and 4 cases of immune-mediated necrotizing myopathy (IMNM). Compared with the healthy control group, the serum levels of dsDNA, IL-1β, and IL-18 were significantly increased in the IIM group and its subgroups (P < 0.05). Except for the fact that there was no statistically significant difference in AIM2 mRNA levels in PBMC of the IMNM subgroup compared to the healthy control group, the expression of AIM2, caspase-1, and GSDMD mRNA was significantly increased in the IIM group and other subgroups (P < 0.05); Except for the comparison of IL-1β mRNA levels in PBMC of the IMNM and OM subgroups with the healthy control group showing no statistical difference, the expression of IL-1β and IL-18 mRNA was significantly increased in the IIM group and other subgroups (P < 0.05); Comparisons between subgroups indicated that the expression of IL-1β mRNA in the DM subgroup was significantly higher than that in the OM and IMNM subgroups, and the expression of IL-18 mRNA in the PM subgroup was significantly higher than that in the DM and OM subgroups (P < 0.05). The expression levels of AIM2, caspase-1, GSDMD, IL-1β, and IL-18 proteins in PBMC of the IIM group and its subgroups were significantly higher than those in the healthy control group (P < 0.05); Comparisons among subgroups revealed that the expression of IL-18 protein in the OM subgroup was significantly higher than that in the PM subgroup (P < 0.05). In the IIM group, the mRNA of caspase-1, GSDMD, and IL-18 showed a positive correlation with AIM2 mRNA, and the protein expression of caspase-1, GSDMD, IL-1β, and IL-18 also showed a positive correlation with AIM2 protein expression. The AIM2 inflammasome-mediated pyroptosis pathway may be involved in the pathogenesis of IIM, providing a theoretical basis for further research on the etiology of IIM and the development of new therapies.
cell therapies
2026-07-13 | POLYMYOSITIS ASSOCIATED WITH PRIMARY BILIARY CIRRHOSIS AND OVARIAN CARCINOMA – CLINICAL CASE PRESENTATION AND LITERATURE REVIEW
Polymyositis is an idiopathic inflammatory myopathy classified under a heterogeneous group of autoimmune diseases predominantly presenting with symmetrical proximal muscle weakness, weakness of neck muscles with the manifestation of a "dropped head" symptom, dysphagia, dysphonia; elevated serum levels of creatine kinase (CK), sometimes in conjunction with elevated liver enzymes; characteristic EMG findings and muscle biopsy. The presence of myositis-specific antibodies in more than half of the patients facilitates the definition of distinct clinical subtypes and aids in accurate diagnosis, with an associated higher risk of involvement of other organs and systems such as the lungs, heart, liver, etc., most commonly presenting as interstitial pulmonary fibrosis, cardiomyopathy, and significantly less frequently primary biliary cirrhosis. A twofold increase in malignancies has been established compared to the general population, or the manifestation of myositis can be presented as a paraneoplastic syndrome. The first-line treatment method is the administration of intravenous corticosteroids in moderate or high doses combined with cytostatic therapy, with rare necessity for intravenous immunoglobulin administration, while plasmapheresis is considered an inapplicable method. We report a case of polymyositis with characteristic clinical and serological findings, with severe respiratory failure, developing twice in the absence of interstitial pulmonary fibrosis, primarily secondary myocardial damage during disease activity, and the presence of asymptomatic ovarian cancer and primary biliary cirrhosis discovered during the course of the disease, demonstrating the best therapeutic effectiveness from plasmapheresis. Accurate diagnosis relies on clinical, electrophysiological, and immunological findings, posing diagnostic challenges and questions that require the collaborative efforts of a multidisciplinary team.
2026-05-19 | Chimeric antigen receptor T-cell (CAR-T) therapy and other cellular immunotherapy treatments for idiopathic inflammatory myopathies.
Idiopathic inflammatory myopathies (IIM), including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), anti-synthetase syndrome (ASyS), overlap myositis and polymyositis, are heterogeneous autoimmune diseases characterized by immune-mediated skeletal muscle injury and frequent extra-muscular organ involvement. Despite recent therapeutic advances, many IIM patients have persistent disease activity, medication toxicity, or steroid dependence with current treatments. Increasing evidence implicates autoreactive B cells and autoantibody-producing plasma cells as central drivers of disease activity in several IIM subtypes, providing a strong rationale for B-cell- targeted therapies. While monoclonal antibody-based B-cell depletion strategies such as rituximab have demonstrated variable efficacy, their inability to effect persistent, intense depletion of tissue autoreactive B-cell populations often limit their success. Chimeric antigen receptor T-cell (CAR-T) and related cellular immunotherapies were originally developed against hematologic malignancies, but have recently emerged potentially transformative therapeutic options for autoimmune diseases. CAR-T cells targeting CD19 and other B-cell antigens have demonstrated the capacity to induce deep and durable B-cell depletion, and may even lead to "immune reset" with long-lived autoimmunity remission in diseases such as systemic lupus erythematosus and systemic sclerosis. Early clinical experiences now suggest that CAR-T therapy may offer similar promise in refractory IIM, particularly in phenotypes that include pathogenic autoantibodies, such as ASyS, DM, IMNM. This review provides a synopsis of current knowledge on the immunopathogenesis of IIM relevant to CAR-T and other cellular immunotherapy, outlines CAR-T technology and the mechanistic rationale for its use in IIM, and critically appraises emerging clinical CAR-T treatment data in IIM. We also discuss safety considerations, practical challenges, and future directions, with a focus on how CAR-based immunotherapies may reshape treatment paradigms for refractory inflammatory myopathies.
2026-05-18 | Case Report: Sustained immune and pulmonary recovery three years after hematopoietic stem cell transplantation for ITCH E3 ubiquitin ligase deficiency.
Itchy E3 ubiquitin ligase deficiency (ITCH deficiency) is a rare monogenic immune dysregulation syndrome characterized by early-onset multisystem autoimmunity and significant morbidity and mortality. Only one prior case report has described a patient treated with hematopoietic stem cell transplantation (HSCT) with clinical improvement, and no established disease-modifying or curative therapy algorithm exists. We describe a female patient who presented in early childhood with chronic lung disease requiring tracheostomy and long-term mechanical ventilation and later developed progressive muscle weakness. She was diagnosed with steroid-responsive juvenile polymyositis and subsequently accumulated multiple autoimmune manifestations including autoimmune hepatitis, enteropathy, psoriasis, inflammatory arthritis, and Sjögren's-like parotitis. Genetic testing ultimately identified compound heterozygous pathogenic variants in ITCH. Despite prolonged treatment with multiple immunosuppressive and biologic therapies, she remained prednisone dependent with poor disease control and substantial treatment-related morbidity. At 20 years of age, she underwent allogeneic hematopoietic stem cell transplantation. Following transplantation, she achieved sustained resolution of autoimmune disease activity, was successfully weaned from all immunosuppressive therapy, and was decannulated from chronic mechanical ventilation, with marked improvement in functional status and quality of life. This is the second reported case demonstrating the benefit of hematopoietic stem cell transplant (HSCT) in ITCH deficiency and provides evidence of durable multisystem clinical remission and recovery of long-standing pulmonary and musculoskeletal disease. These findings support consideration of HSCT as a therapeutic option in carefully selected patients with severe, refractory autoimmune manifestations due to ITCH deficiency and raise the possibility that earlier consideration in the disease course may mitigate cumulative disease- and treatment-related morbidity.
2025-05-12 | Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases.
Rheumatic diseases are chronic immune-mediated disorders affecting multiple organ systems and significantly impairing patients' quality of life. Current treatments primarily provide symptomatic relief without offering a cure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their ability to differentiate into various cell types and their immunomodulatory, anti-inflammatory, and regenerative properties. This review aims to summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions. A comprehensive review of preclinical and clinical studies on MSC therapy in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis, Sjögren's syndrome, Crohn's disease, fibromyalgia, systemic sclerosis, dermatomyositis, and polymyositis, was conducted. Emerging strategies to enhance MSC efficacy and overcome current limitations were also analyzed. Evidence from preclinical and clinical studies suggests that MSC therapy can reduce inflammation, modulate immune responses, and promote tissue repair in various rheumatic diseases. Clinical trials have demonstrated potential benefits, including symptom relief and disease progression delay. However, challenges such as variability in treatment response, optimal cell source and dosing, long-term safety concerns, and regulatory hurdles remain significant barriers to clinical translation. Standardized protocols and further research are required to optimize MSC application. MSC therapy holds promise for managing rheumatic diseases, offering potential disease-modifying effects beyond conventional treatments. However, large-scale, well-controlled clinical trials are essential to establish efficacy, safety, and long-term therapeutic potential. Addressing current limitations through optimized treatment protocols and regulatory frameworks will be key to its successful integration into clinical practice.
2025-03-24 | Carbamoyl phosphate synthetase 1 deficiency manifested in an adult treated with prednisone for polymyositis, and cured by live-donor liver transplantation.
Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM#237300) is a rare inherited disorder due to complete or partial lack of the CPS1 enzyme. Polymyositis is a relatively rare systemic inflammatory autoimmune disease. Here, we report a 59-year-old Japanese woman diagnosed with late-onset CPS1 deficiency during polymyositis treatment. The polymyositis appeared two years before the diagnosis of CPS1 deficiency. Prednisolone (PSL) at 35 mg/day initial dosage, promptly alleviated the symptoms. However, the patient, without apparent cause, suddenly developed confusion progressing to unconsciousness and coma. Upon admission, the patient's plasma ammonia levels were 458 μg/dL (269 μM). Plasma amino acid analysis revealed decreased citrulline levels and elevated glutamine levels. Genetic analysis of CPS1 (OMIM *608307) showed homozygosity for the likely pathogenic variant c.2397G > A (p.Met799Ile), leading to the diagnosis of CPS1 deficiency. The patient responded to pharmacotherapy and continuous hemodialysis. However, the patient experienced hyperammonemia decompensation events while on pharmacotherapy at home, which were successfully managed with emergency treatment and/or hemodialysis. Subsequently, after liver transplantation, the patient's plasma ammonia levels consistently remained at normal. This case illustrates late-onset CPS1 deficiency manifested in an adult treated with PSL for polymyositis, and the cure of its enzyme deficiency by live-donor liver transplantation.
proteins
2026-06-25 | Acthar Gel treatment in patients with rheumatoid arthritis, systemic lupus erythematosus, or dermatomyositis/polymyositis: analysis of physician-reported charts.
Aim: To examine the characteristics, treatment patterns, and physicians' assessments of outcomes for patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or dermatomyositis/polymyositis (DM/PM) who received Acthar Gel. Materials & methods: This survey-based medical chart review study asked rheumatologists who met specific inclusion criteria to abstract data from patient records covering the period from April 2022 to November 2024. Eligible patients were adults ≥18 years diagnosed with RA, SLE, or DM/PM, treated with Acthar Gel for ≤24 months. An online questionnaire screened and identified contributing physicians and collected anonymized patient data (baseline demographic, medical history, concomitant medications, Acthar Gel treatment history, and physicians' assessment of health status, symptom severity, treatment outcomes with Acthar Gel). Results: The study population comprised 73 patients with RA (average age 50 years; 49 [67%] female; 44 [60%] White/non-Hispanic), 56 with SLE (average age 42 years; 47 [84%] female; 28 [50%] African-American), and 104 with DM/PM (average age 52 years; 69 [66%] female; 62 [60%] White/non-Hispanic). Patients had received Acthar Gel for an average of 9 (RA) or 8 months (SLE, DM/PM), with most receiving treatment at the time of the study. Per physicians' assessment, health status improved in 68 (93%) patients with RA, 50 (89%) patients with SLE, and 100 (96%) patients with DM/PM after starting treatment with Acthar Gel. The most common treatment goals achieved in patients with improved overall health status were improved overall symptoms, pain, physical function, and corticosteroid use in the RA cohort; overall symptoms, pain, corticosteroid use, and fatigue in the SLE cohort; and overall symptoms, strength, physical function, and corticosteroid use in the DM/PM cohort. Conclusion: These findings support the use of Acthar Gel as a potential treatment option for appropriate patients with RA, SLE, or DM/PM.
2026-03-26 | Interleukin-2 Deprived State of Regulatory T cells and Their Recovery by Low-Dose Interleukin-2 in Patients With Inflammatory Myopathies.
Regeneration and expansion of Treg by low-dose interleukin-2 (IL-2) therapy is considered a potential treatment strategy for a wide range of autoimmune diseases. To provide a pathophysiologically-based rationale for low-dose IL-2 therapy, we investigated whether reversible defects in the Treg-IL-2 axis emerge in inflammatory myopathies. CD4+ T cell subsets from patients with polymyositis (PM) or dermatomyositis (DM) (n = 20) and healthy controls (HC) (n = 19) and peripheral blood mononuclear cells (PBMC) from eight patients that were stimulated in vitro for 24 hours with different concentrations of recombinant human IL-2 were analyzed by multicolor flow cytometry. Messenger RNA (mRNA) expressions of IL2RA, IL2RB, IL2RB, ENTPD1, IKZF2, and CTLA4 were quantified by real-time polymerase chain reaction in IL-2 stimulated PBMC (n = 6). Two patients with refractory PM/DM were treated with low-dose IL-2 therapy for eight weeks and monitored for clinical responses and changes in Treg subsets. Frequencies of Treg expressing CD25 at high levels (CD25hi Treg) and of CXCR5+ Treg were reduced in patients with PM/DM compared with HC (P = 0.0052; P = 0.0661), particularly in active myositis (P = 0.0036; P = 0.0335). Stimulation with low doses of IL-2 selectively enhanced expression of CD25 molecules by Treg, leading to an increase in the CD25hi Treg subset (P < 0.05) and augmented mRNA expression of several immunoregulatory molecules (P < 0.05). Low-dose IL-2 therapy induced decreases in muscle enzymes that were accompanied by a sustained expansion of CD25+ Treg. Our data suggest that shortage of IL-2 is pathophysiologically relevant in PM/DM. Recovery and expansion of Treg by low-dose IL-2 therapy could thus be a promising targeted treatment option.
2026-02-13 | [Macrophage activation syndrome in a young patient with polymyositis].
Haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) is a life-threatening condition characterised by systemic hyperinflammation and is often triggered by infections, malignancies, or autoimmune disease. The HScore is a diagnostic tool used to estimate the likelihood of HLH/MAS based on clinical, biochemical, and histological findings. This case describes a patient with polymyositis developing MAS, indicated by an HScore of 219. He was treated with IV anakinra, steroids, and immunoglobulin, leading to significant improvement. This case emphasises the importance of early MAS recognition and timely intervention in critical conditions.
2024-03-25 | Pathogenicity of functionally activated PD-1+CD8+ cells and counterattacks by muscular PD-L1 through IFNγ in myositis.
Programmed-cell-death 1 (PD-1) expression is associated not only with T-cell activation but with exhaustion. Specifically, PD-1+ T cells present an exhausted phenotype in conditions of chronic antigen exposure, such as tumor microenvironments and chronic viral infection. However, the immune status regarding exhaustion of PD-1+CD8+ T cells in chronic autoimmune diseases including idiopathic inflammatory myopathies (IIMs) remains unclear. We aimed to clarify the role of PD-1+CD8+ T cells and PD-1 ligand (PD-L1) in IIMs. We showed that PD-1+ cells infiltrated into PD-L1-expressing muscles in patients with IIMs and immune checkpoint inhibitor-related myopathy. According to the peripheral blood immunophenotyping, the PD-1+CD8+ cell proportions were comparable between the active and inactive patients. Of note, PD-1+CD8+ cells in the active patients highly expressed cytolytic molecules, indicating their activation, while PD-1-CD8+ cells expressed low levels of cytolytic molecules in the active and inactive patients. A part of PD-1+CD8+ cells expressed the HMG-box transcription factor TOX highly and presented the exhausted phenotype in the active patients. Among PD-1+CD4+ T cells, PD-1highCXCR5-CD45RO+CD4+ peripheral helper T cells were increased in the active patients. PD-L1-deficient mice developed severer C-protein-induced myositis (CIM), a model of polymyositis, with abundant infiltration of PD-1+CD8+ cells expressing cytolytic molecules than wild-type mice, indicating pathogenicity of the PD-1+CD8+ cells and the protective role of PD-L1. The deficiency of IFNγ, a general PD-L1-inducer, impaired muscular PD-L1 expression and exacerbated CIM, indicating IFNγ-dependent muscular PD-L1 regulation. IFNγ-induced PD-L1 on myotubes was protective in an established muscle injury model. In conclusion, PD-1+CD8+ T cells rather than PD-1-CD8+ T cells were a pathogenic subset of IIMs. Muscular PD-L1 was regulated by IFNγ and exerted protective properties in IIMs.
2023-12-28 | Polymyositis following varicella and mumps infection in adults: report of two cases.
Idiopathic immune myopathies (IIMs) are autoimmune diseases caused by immune-mediated muscle damage. The etiology remains unclear. Epidemiological and experimental studies, both in animals and humans, hint at viruses as major environmental factors able to trigger aberrant immune responses through many different mechanisms. However, only a few cases of either dermatomyositis or polymyositis following a specific viral infection have been reported in the literature. The objective of this study is to describe the clinical features and the treatment strategy of 2 cases of polymyositis developing shortly after chickenpox and mumps, respectively, and to review the existing literature on the topic. The clinical records of the 2 patients suspected to have developed inflammatory myositis following a viral infection were reviewed. Their clinical history, main laboratory findings, and treatment outcome are presented here. Moreover, a literature search was performed in the PubMed and MEDLINE databases to identify reports describing the association between viral infections and IIMs in patients aged ≥18. The 2 patients reported here developed polymyositis shortly after chickenpox and mumps, respectively, suggesting a causal role for viruses in triggering autoimmunity. Only a few reports published between 1990 and 2020 were found in the literature, possibly linking infections to myositis development. Intravenous immunoglobulin and rituximab were effective for the treatment of viral-triggered polymyositis.
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2026-08-10 | Outcomes of Immune Check Point Inhibitor Use in US Veterans With Pre-Existing Idiopathic Inflammatory Myopathies: Case Series and Literature Review.
Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre-existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision-making and close monitoring.
2026-08-08 | Pulmonary arterial hypertension in polymyositis: a case report
Pulmonary arterial hypertension (PAH) associated with connective tissue diseases is a lifethreatening condition in which elevated pressure in the pulmonary vasculature leads to a marked increase in right heart afterload, causing severe right ventricular failure and premature death. PAH is most frequently associated with systemic sclerosis and systemic lupus erythematosus. Polymyositis is a rare autoimmune disease resulting from aberrant activation of cytotoxic Tlymphocytes and macrophages against autologous muscle tissue, leading to inflammatory myopathy. In polymyositis, the inflammatory process may involve the vascular bed (small pulmonary artery vasculitis), which can lead to PAH. PAH in polymyositis is an extremely rare entity. This article presents a clinical observation of a patient with idiopathic polymyositis who developed a fatal complication — PAH — over several years. Key diagnostic aspects, clinical course features, and characteristic signs of the disease are demonstrated. The need for a multidisciplinary approach in managing patients with this condition is emphasised, and the importance of accumulating data on pulmonary hypertension in polymyositis is highlighted
2026-08-08 | A systematic review of abatacept and belatacept in immune-mediated diseases.
Abatacept (ABA) and belatacept (BEL) are immunomodulatory fusion proteins in which the extracellular domain of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is linked to the Fc fragment of human IgG1. Functionally, they bind to cell surface antigens CD80 and CD86 on antigen-presenting cells, thereby preventing CD28-mediated costimulatory signaling. This systematic review aims to evaluate the clinical efficacy of ABA and BEL in immune-mediated diseases, focusing on indications currently not approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). We searched PubMed and Web of Science for reports describing clinical efficacy of ABA or BEL in at least one patient with immune-mediated conditions outside FDA/EMA-approved indications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided our data reporting. Of 5333 articles initially extracted, 2778 unique records were screened after de-duplication, and 96 matched our criteria and were included in this study. ABA was beneficial in patients diagnosed with Sjögren's syndrome (particularly secondary forms); autoimmunity in association with immunodeficiency; early, inflammatory and normal-like subtypes of systemic sclerosis; scleroderma; arthritis in systemic lupus erythematosus; inflammatory myopathies (polymyositis, immune-mediated necrotizing myositis, and antisynthetase syndrome); and giant-cell arteritis. Lower-level evidence studies reported positive results using ABA to treat granulomatosis with polyangiitis; relapsing polychondritis; sarcoidosis; and inflammatory eye diseases. Results of several studies highlighted the positive impact of ABA on arthritis in patients taking this drug for other indications. Likewise, several autoimmune diseases responded effectively to ABA when used to treat concomitant rheumatoid arthritis. Positive serological responses suggesting downstream modulation of B cell activation were reported in several randomized controlled trials. BEL was used after kidney transplantation in patients with proteinuric kidney disease or lupus nephritis, and in a few non-transplanted CTLA-4 haploinsufficiency carriers for immunodeficiency-associated autoimmunity. Our results provide a comprehensive summary of the efficacy of ABA and BEL across a broad spectrum of autoimmune diseases.
2026-08-06 | A Case Report on Polymyositis
Polymyositis is a chronic autoimmune inflammatory myopathy marked by symmetrical proximal muscle weakness due to immune-mediated muscle fiber damage.The disease predominantly affects adults, exhibiting a higher incidence in females, and is characterized by immune activation involving cytotoxic T lymphocytes and inflammatory mediators.Polymyositis symptoms include trouble getting up from a chair, climbing stairs, or lifting things. These symptoms are often accompanied by fatigue, muscle pain, trouble swallowing (dysphagia), and possible breathing problems. Patients exhibit progressive muscle weakness, dysphagia, and systemic manifestations which can severely affect quality of life.Diagnosis entails clinical assessment, laboratory analyses including elevated creatine kinase levels, autoantibody testing, imaging modalities, electromyography, and muscle biopsy for validation. The main goal of management is to make muscles stronger and improve functional outcomes through drug treatments. Corticosteroids are the first-line treatment, and immunosuppressive drugs like methotrexate and azathioprine are also used. .To improve the prognosis and the quality of life for patients, it is important to diagnose them early and use a multidisciplinary approach to treatment.
2026-07-08 | The onset of systemic scleroderma in combination with polymyositis (cross-form) after suffering from COVID-19
According to current concepts, immuno-inflammatory rheumatic diseases are similar to COVID-19 in terms of clinical manifestations, immune responses and pathogenetic mechanisms, which is due to the systemic nature of the lesion. In patients with genetic prerequisites, both infection and vaccination against COVID-19 can trigger the immune-inflammatory process. The article presents a clinical observation demonstrating the diagnostic difficulties encountered in the diagnosis of systemic scleroderma and polymyositis that developed after COVID-19. Оnly timely diagnosis and adequate therapy can significantly improve the condition and, consequently, the prognosis of this category of patients. A special feature of this case is the absence of autoimmune markers – immunoblots confirming the diagnosis of systemic scleroderma and polymyositis in the presence of vivid clinical symptoms of each of these diseases. The addition of rituximab to the standard basic therapy increases its effectiveness.
other
2022-03-30 | MicroRNA-409-3p regulates macrophage migration in polymyositis through targeting CXCR4.
Macrophage migration and infiltration contribute to the pathogenesis of polymyositis (PM). This study aims to investigate the effect and underlying mechanism of miR-409-3p on macrophage migration in PM. The GSE143845 database was used to predict the altered expression of microRNAs (miRNAs) in PM. The quantitative real-time PCR (qRT-PCR), western blot and Transwell assay were performed to detect migration of macrophages and expressions of related molecules. A luciferase activity assay was conducted to confirm the binding of miR-409-3p and CXCR4 3'-UTR. Next, a mouse model of experimental autoimmune myositis (EAM) was established. Haematoxylin and eosin (HE) staining, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to measure associated factors. MiR-409-3p was downregulated in PM of GSE143845 database and patients. Differently, the serum creatine kinase (s-CK), TNF-α, and IL-6 in patients with PM were increased. Furthermore, miR-409-3p mimic transfection reduced the migration of macrophages and CXCR4 levels, while miR-409-3p inhibitor exerted the opposite effects. CXCR4 was a target of miR-409-3p, and the effect of CXCR4 on promoting macrophage migration was reversed by miR-409-3p mimic. In vivo, miR-409-3p agomir injection reduced inflammatory cells, macrophages, and TNFα and IL-6 levels in muscles and serum of EAM mouse models. In conclusion, miR-409-3p reduces the migration of macrophages through negatively regulating CXCR4 expression in PM.
2020-05-31 | Muscle Weakness in Myositis: MicroRNA‐Mediated Dystrophin Reduction in a Myositis Mouse Model and Human Muscle Biopsies
Objective Muscle inflammation is a feature in myositis and Duchenne muscular dystrophy ( DMD ). Autoimmune mechanisms are thought to contribute to muscle weakness in patients with myositis. However, a lack of correlation between the extent of inflammatory cell infiltration and muscle weakness indicates that nonimmune pathologic mechanisms may play a role. The present study focused on 2 micro RNA (mi RNA ) sets previously identified as being elevated in the muscle of patients with DMD —an “inflammatory” mi RNA set that is dampened with glucocorticoids, and a “dystrophin‐targeting” mi RNA set that inhibits dystrophin translation—to test the hypothesis that these mi RNA s are similarly dysregulated in the muscle of patients with myositis, and could contribute to muscle weakness and disease severity. Methods A major histocompatibility complex class I–transgenic mouse model of myositis was utilized to study gene and mi RNA expression and histologic features in the muscle tissue, with the findings validated in human muscle biopsy tissue from 6 patients with myositis. Mice were classified as having mild or severe myositis based on transgene expression, body weight, histologic disease severity, and muscle strength/weakness. Results In mice with severe myositis, muscle tissue showed mononuclear cell infiltration along with elevated expression of type I interferon and NF ‐κB–regulated genes, including Tlr7 (3.8‐fold increase, P < 0.05). Furthermore, mice with severe myositis showed elevated expression of inflammatory mi RNA s (miR‐146a, miR‐142‐3p, miR‐142‐5p, miR‐455‐3p, and miR‐455‐5p; ~3–40‐fold increase, P < 0.05) and dystrophin‐targeting mi RNA s (miR‐146a, miR‐146b, miR‐31, and miR‐223; ~3–38‐fold increase, P < 0.05). Bioinformatics analyses of chromatin immunoprecipitation sequencing (ChIP‐seq) data identified at least one NF ‐κB consensus element within the promoter/enhancer regions of these mi RNA s. Western blotting and immunofluorescence analyses of the muscle tissue from mice with severe myositis demonstrated reduced levels of dystrophin. In addition, elevated levels of NF ‐κB–regulated genes, TLR 7 , and mi RNA s along with reduced dystrophin levels were observed in muscle biopsy tissue from patients with histologically severe myositis. Conclusion These data demonstrate that an acquired dystrophin deficiency may occur through NF ‐κB–regulated mi RNA s in myositis, thereby suggesting a unifying theme in which muscle injury, inflammation, and weakness are perpetuated both in myositis and in DMD .
2020-02-21 | Reduced miR-146a Promotes REG3A Expression and Macrophage Migration in Polymyositis and Dermatomyositis
Background: Growing evidence from studies elsewhere have illustrated that microRNAs (miRNAs) play important roles in Polymyositis and Dermatomyositis (PM/DM). However, little has been reported on their relationship with regenerating islet-derived protein 3-alpha (REG3A) as well as their associative roles in macrophage migration. Therefore, this study sought to establish the association between miR-146a and REG3A as well as investigate their functional roles in macrophage migration and PM/DM pathogenesis. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from PM/DM patients and healthy controls through density centrifugation. Macrophages were obtained from monocytes purified from PBMCs via differentiation prior to their transfection with microRNA (miRNA) or plasmids to investigate cell migration with transwell assay. An experimental autoimmune myositis (EAM) murine model was used to investigate PM/DM. Real-time PCR and western blot analysis were conducted to determine the expression levels of miR-146a, IFN-γ, IL-17A and REG3A. Results: The mRNA expression level of miR-146a markedly decreased while the mRNA level of REG3A, IFN-γ and IL-17A expression increased substantially in PBMCs from PM/DM patients compared with the healthy controls. The levels of IFN-γ and IL-17A in serum from PM/DM patients was much higher than the healthy controls. Immunohitochemistry analysis showed that REG3A expression increased in muscle tissues from patients. Consistent with clinical data, the mRNA expression level of miR-146a also decreased whereas the mRNA and protein level of REG3A, IFN-γ and IL-17A significantly increased in the muscle tissues of EAM mice. Moreover, miR-146a inhibited monocyte-derived macrophage migration and REG3A promoted macrophage migration. In addition, IL-17A induced REG3A expression, while miR146a inhibited expression of REG3A in monocyte-derived macrophages from the PBMCs of the healthy donors. Notably, inhibition of macrophage migration by miR-146a was via the reduction of REG3A expression. Conclusions: Reduced miR-146a expression in PM/DM leads to increased REG3A expression that increases inflammatory macrophage migration, which may be a possible underlying mechanism of DM/PM pathogenesis.
2018-06-29 | MicroRNA-381 reduces inflammation and infiltration of macrophages in polymyositis via downregulating HMGB1
The downregulation of microRNA (miR)-381 has been detected in various diseases. The present study aimed to investigate the effects, and underlying mechanisms of miR-381 on inflammation and macrophage infiltration in polymyositis (PM). A mouse model of experimental autoimmune myositis (EAM) was generated in this study. Hematoxylin and eosin staining was conducted to detect the inflammation of muscle tissues. In addition, ELISA and immunohistochemistry were performed to determine the expression levels of associated factors, and reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression levels of related mRNAs and proteins. A luciferase activity assay was used to confirm the binding of miR-381 and high mobility group box 1 (HMGB1) 3' untranslated region. Transwell assays were also performed to assess the migratory ability of macrophages. The results demonstrated that serum creatine kinase (s-CK), HMGB1 and cluster of differentiation (CD)163 expression in patients with PM were increased compared within healthy controls. Conversely, the expression levels of miR-381 were downregulated in patients with PM. Furthermore, high HMGB1 expression was associated with poor survival rate in patients with PM. In the mouse studies, muscle inflammation and CD163 expression were decreased in the anti-IL-17 and anti-HMGB1 groups, compared with in the EAM model group. The expression levels of s-CK, HMGB1, IL-17 and intercellular adhesion molecule (ICAM)-1 were also downregulated in response to anti-IL-17 and anti-HMGB1. These findings indicated that HMGB1 was closely associated with inflammatory responses. In addition, the present study indicated that transfection of macrophages with miR-381 mimics reduced the migration of inflammatory macrophages, and the expression levels of HMGB1, IL-17 and ICAM-1. Conversely, miR-381 inhibition exerted the opposite effects. The effects of miR-381 inhibitors were reversed by HMGB1 small interfering RNA. In conclusion, miR-381 may reduce inflammation and the infiltration of macrophages; these effects were closely associated with the downregulation of HMGB1.
2017-02-13 | MiR-146a Regulates Inflammatory Infiltration by Macrophages in Polymyositis/Dermatomyositis by Targeting TRAF6 and Affecting IL-17/ICAM-1 Pathway.
The primary objective of this study was to investigate the role of miR-146a in inducing the inflammatory infiltration of macrophages in polymyositis/dermatomyositis (PM/DM) through targeting TNF receptor associated factor 6 (TRAF6), which may further down-regulate the Interleukin-17 (IL-17)/Intercellular Adhesion Molecule 1 (ICAM-1) pathway. Biopsies were collected from PM/DM patients and healthy volunteers. PM/DM model establishment and macrophage isolation were performed on Sprague Dawley (SD) rats. Model rats and macrophages were treated with anti-IL-17, anti-ICAM-1, miR-146a mimics, miR-146a inhibitors, and TRAF6 siRNAs. Serum creatine phosphokinase (S-CK) expression was assessed using double antibody sandwich enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry assay was performed to analyze CD163 expression in muscle samples. Furthermore, we used transwell assay to test cell migration; RT-PCR and western blot were carried out to determine the expression of miR-146a, TRAF6, IL-17, and ICAM-1. The S-CK, TRAF6, IL-17 and ICAM-1 levels were higher in PM/DM patients compared with healthy controls and were down-regulated after the conventional treatment. Treatment with miR-146a mimics, anti-IL-17 and anti-ICAM-1 decreased the expression of IL-17 and ICAM-1, whereas miR-146a inhibitors exerted the opposite effects. The effects of miR-146a inhibitors were suppressed by treatment with TRAF6 siRNA. In addition, the luciferase reporter assay validated the targeting relationship between miR-146a and TRAF6. MiR-146a regulates inflammatory macrophage infiltration in PM/DM by targeting TRAF6 and affecting the IL-17/ICAM-1 pathway.
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Drug Discovery Landscape
6 orphan drug designations for Polymyositis.
6 orphan drug designations for Polymyositis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Glucagon like peptide-1 (GLP-1) Elastin like peptide (ELP)-120 fusion protein | proteins | FDA | 2021-08-31 | — | ImmunoForge Co., Ltd. |
(2S,3R)-N-[(2S)-3-(cyclopent-1-en-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]propanamido]propanamide maleate | small molecules | FDA | 2020-10-21 | — | Kezar Life Sciences, Inc. |
Siponimod [BAF312] | small molecules | EMA | 2014-11-19 | — | Novartis Europharm Limited |
Siponimod | small molecules | FDA | 2013-11-26 | — | Novartis Pharmaceuticals Corporation |
Human normal immunoglobulin [Gammagen] | antibodies | EMA | 2003-10-24 | — | [INACTIVE] Orfagen |
Immune globulin intravenous (human) | antibodies | FDA | 1992-10-13 | — | Immuno Clinical Research Corp. |
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