RARE DISEASE
Granulomatosis with polyangiitis
Granulomatosis with polyangiitis
Granulomatosis with polyangiitis
Synonyms: GPA
Synonyms: GPA
Synonyms: GPA
Drug discovery
4
drugs
With orphan designations
Overview
Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated vasculitis characterized by necrotizing inflammation of small-to-medium vessels, granuloma formation, and frequent involvement of the upper/lower respiratory tracts and kidneys [1][4][19]. Diagnosis relies on clinical presentation, ANCA serology (primarily PR3-ANCA), and histopathology [10][19]. Untreated mortality exceeds 80%, but modern regimens reduce this to ~10% [4][19].
Population
Incidence: 3-14.4 cases/million annually in Europe, 12.8/million in U.S. working-age adults [2][12][16]
Demographics: Peak onset 40-65 years; slight male predominance (1.2:1). More common in Caucasians (~90% of cases) [2][7][19]
Pediatric: Rare (1.8/million incidence), higher hematologic complications vs adults [12][19]
Burden
Morbidity: 35-44% relapse rate; chronic kidney disease in 20-25%, hearing loss in 22-42% [4][6][12]
Mortality: 10% at 5 years (vs 80% untreated), often from infections or cardiovascular events [4][19]
Economic: Annual costs ~$78,000/patient with relapses vs $27,000 in remission [9]. Pediatric patients incur 2-3× higher hospitalization rates [12].
Therapies
Induction: High-dose glucocorticoids + rituximab (preferred) or cyclophosphamide for severe disease [1][3][19]
Maintenance: Rituximab monotherapy or methotrexate/azathioprine for 12-24 months [1][19]
Emerging: Avacopan (complement C5a inhibitor) reduces steroid exposure [1], plasma exchange reserved for refractory cases [1][19]
Categories: rare circulatory system diseases, rare neurological diseases, rare renal diseases, rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
2,011 drug discovery papers about Granulomatosis with polyangiitis, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2,011 drug discovery papers about Granulomatosis with polyangiitis, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-07 | Hepatic granulomas as a manifestation of ANCA-associated vasculitis:a systematic review.
ANCA-associated vasculitides (AAV) - granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) - are rare small-vessel autoimmune diseases. Liver involvement in AAV is uncommon and generally manifests as biochemical hepatitis; true hepatic granulomatosis is exceedingly rare and diagnostically challenging. We conducted a systematic scoping review following PRISMA-ScR guidelines and the Arksey & O'Malley framework, searching PubMed, Google Scholar, ScienceDirect, and Scopus without date restriction (through March 2026). A total of 7, 033 records were initially retrieved; after deduplication, title/abstract screening, and full-text review, five articles meeting strict inclusion criteria were included for qualitative synthesis. Five published cases of hepatic granulomas in AAV patients with no confirmed confounding etiology were identified. All were GPA or EGPA; no case of pure MPA was documented. Three patients were female and two were male, with a mean age of 57.6 years. Liver histology revealed non-necrotizing epithelioid granulomas (n = 2), granulomatous inflammation with necrosis (n = 1), incomplete septal cirrhosis with vasculopathic changes (n = 1), and incidental calcified granulomas (n = 1). Immunosuppressive therapy with corticosteroids and/or cyclophosphamide achieved clinical and biochemical improvement in all treated patients. Hepatic granulomatosis is a rare but genuine extra-respiratory manifestation of AAV, most frequently reported in GPA. It may antedate the canonical ENT-pulmonary-renal triad, presenting as incidental hepatomegaly or unexplained liver function test elevation. Systematic exclusion of competing etiologies (sarcoidosis, tuberculosis, primary biliary cholangitis, drug-induced hepatitis) is mandatory before attributing granulomas to AAV. Liver biopsy remains pivotal in confirming the diagnosis. Immunosuppression is the therapeutic cornerstone, with generally favourable outcomes.
2026-08-05 | Anterior ischaemic optic neuropathy as an initial manifestation of eosinophilic granulomatosis with polyangiitis: The importance of early and appropriate immunosuppressive treatment for visual recovery.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody-associated vasculitis, affecting various organs. Although ocular involvement occurred in 6.8-11.1% of patients, anterior ischaemic optic neuropathy (AION) is rare. We present the case of a 57-year-old woman with an 11-year history of asthma who developed sudden, painless visual loss in her left eye. On admission (3 days after symptom onset), visual acuity was counting fingers in the left eye and 20/20 in the right eye. Funduscopy showed left optic disc oedema. Magnetic resonance imaging revealed intravitreal protrusion of the left optic nerve head with restricted diffusion and local contrast enhancement of the left intraorbital and retrobulbar fat. Given also peripheral eosinophilia, myeloperoxidase-antineutrophil cytoplasmic antibody positivity, mononeuritis multiplex, nasal polyps, sinusitis, and pulmonary involvement, EGPA with AION was diagnosed. Intravenous methylprednisolone pulse was urgently administered, followed by mepolizumab 2 weeks later. Although eosinophilic inflammation and imaging findings improved, visual acuity remained unchanged over 1 year. A literature review identified 14 cases of EGPA-associated AION. Including our case, 11 cases with available data (14 eyes) were analysed. Overall, visual recovery was observed in 29%. Among 12 eyes with severe visual impairment before treatment, visual recovery occurred only in those treated earlier or with cyclophosphamide except for one, whereas no recovery occurred in those with delayed treatment or without cyclophosphamide. This case highlights the potential of AION as an initial manifestation of EGPA. Both earlier initiation and adequate intensity of immunosuppressive therapy, particularly including cyclophosphamide when clinically appropriate, may be important for visual recovery in EGPA-associated severe AION.
2026-07-28 | Advances in the Diagnosis, Treatment and Prognosis of ANCA-Associated Glomerulonephritis.
ANCA-associated vasculitis (AAV) with kidney involvement represents small-vessel vasculitis, characterized by rapidly progressive glomerulonephritis and a high risk of end-stage kidney disease (ESKD) and increased mortality. AAV typically presents with multisystem involvement, with renal manifestations occurring more frequently in microscopic polyangiitis (MPA) (90-100%) and granulomatosis with polyangiitis (GPA) (50-80%). The classic clinical presentation includes acute kidney injury with hematuria and proteinuria, accompanied by ANCA positivity (MPO-ANCA or PR3-ANCA). Histologically, the predominant pattern is segmental necrotizing glomerulonephritis with crescent formation. Treatment consists of two phases: (a) induction of remission with a lower cumulative dose of glucocorticoids (according to the reduced-dose PEXIVAS regimen) in combination with rituximab or cyclophosphamide and (b) maintenance of remission with rituximab for 2-4 years. The C5a receptor inhibitor avacopan can be used as a steroid-sparing agent in patients with severe kidney involvement or at high risk of corticosteroid-related complications. Beyond the traditional markers of disease activity (hematuria, proteinuria, eGFR), novel biomarkers such as urinary soluble CD163, MCP-1, complement activation products (C5a, sC5b-9), and urinary Treg/Th17 profiles have demonstrated prognostic value. Early diagnosis and prompt initiation of immunosuppressive therapy significantly improve both kidney and overall survival, while prevention of relapses and long-term complications plays a key role in improving the long-term prognosis of patients with AAV.
2026-06-25 | No benefit of adding glucocorticoids to maintenance treatment in reducing the risk of major relapses in ANCA-associated vasculitis: real life data from a longitudinal cohort study.
To examine the role of low-dose glucocorticoids (GCs) in major relapse, hospitalisation and damage accumulation risk during maintenance therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs). Retrospective cohort study of newly diagnosed patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) followed in three tertiary referral centres. We recorded relapses (Birmingham Vasculitis Activity Score increase >0), increases in Vasculitis Damage Index (VDI) and hospitalisations. We used time-varying and mixed-effects Cox models to examine the effect of GCs on the risk of major relapses, VDI accumulation and hospitalisations. Sensitivity analysis was also conducted to address potential confounding. 171 patients (GPA: 107, MPA: 64, median age: 61 years) were included with a median follow-up of 88.2 months (803.4 patient years (PY)). We recorded 65 major relapses (8.1/100 PY) in 48 patients (28%), 65 events of new damage (8.1/100 PY) and 132 hospitalisations (16.4/100 PY). By multivariable analysis, rituximab use was associated with a lower risk (HR=0.21, 95% CI 0.09 to 0.47, p=0.0001) while disease activity at diagnosis was associated with an increased risk (HR=1.17, 95% CI 1.03 to 1.33, p=0.013) of major relapses. Low-dose GCs were not associated with a reduced major relapse risk (HR=0.96, 95% CI 0.88 to 1.05, p=0.36) but they were associated with a risk of damage accumulation (HR=1.52, 95% CI 1.19 to 1.93, p=0.0007) and hospitalisations (HR=1.24, 95% CI 1.06 to 1.45, p=0.006). Higher GC exposure during maintenance therapy was not significantly associated with a lower major relapse risk whereas it was associated with damage accrual and hospitalisation. These findings may support decision making regarding long-term GC use in patients with GPA/MPA.
2026-06-05 | Early relapse under the LoVAS reduced-dose glucocorticoid regimen in ANCA-associated vasculitis: a single-center retrospective observational study.
To evaluate early relapse and other clinical outcomes in patients with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) treated with reduced-dose glucocorticoid (GC) regimens, with a focus on the LoVAS regimen in comparison with the PEXIVAS regimen. We conducted a retrospective single-center cohort study of consecutive patients with newly diagnosed or relapsing MPA or GPA treated between March 2022 and September 2025. Patients were classified into LoVAS or PEXIVAS groups if they adhered to the assigned reduced-dose GC regimens for at least 14 days. The primary outcome was time to first relapse. Secondary outcomes included time to GC withdrawal, time to serious adverse events, and cumulative GC exposure. Time-to-event outcomes were analyzed descriptively using Kaplan-Meier curves and log-rank tests and were interpreted as exploratory because of the small sample size and limited number of events. A total of 21 patients were included (LoVAS, n = 5; PEXIVAS, n = 16). Relapse occurred in 3/5 patients in the LoVAS group and 2/16 patients in the PEXIVAS group. In the LoVAS group, relapses occurred on days 21, 52, and 128 after treatment initiation. GC was withdrawn in 5/5 patients in the LoVAS group and 5/16 patients in the PEXIVAS group. Serious adverse events occurred in 3/5 patients in the LoVAS group and 7/16 patients in the PEXIVAS group. The median average daily prednisolone-equivalent dose was lower in the LoVAS group than in the PEXIVAS group: 3.06 mg/day versus 14.5 mg/day. These findings were interpreted descriptively because of the small sample size and limited number of events. These findings should be interpreted as hypothesis-generating and suggest that early relapse may occur in some patients treated with the LoVAS regimen in real-world practice. Further studies with larger cohorts and appropriate adjustment for confounding factors are needed.
cell therapies
2026-05-14 | ANCA vasculitis: what is in the pipeline.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is now recognized as a complex immune-mediated inflammatory disorder rather than a purely pauci-immune small-vessel vasculitis. Advances in understanding ANCA specificity, complement activation, neutrophil extracellular trap formation, genetic susceptibility, and environmental triggers have reshaped concepts of disease classification, prognosis, and therapy. A focused review of these developments is timely because they are directly informing current treatment strategies, disease stratification, and future drug development. Treatment has shifted from conventional cyclophosphamide and glucocorticoids toward targeted, steroid-sparing approaches. Rituximab is now central to remission induction and maintenance, while avacopan in GPA (granulomatosis with polyangiitis) and MPA (microscopic polyangiitis) and interleukin (IL)-5 blockade in EGPA (eosinophilic granulomatosis with polyangiitis) further reduce glucocorticoid exposure and toxicity. Emerging therapies include next-generation anti-CD20 monoclonal antibodies such as obinutuzumab, CAR-T cell strategies, and other precision immunologic approaches targeting B-cell pathways, including BAFF/APRIL blockade, tyrosine kinase inhibitors (TKIs) and complement-directed therapies designed to more selectively interrupt pathogenic inflammation. Improved biologic insight is enabling biomarker-driven classification and mechanism-based therapy selection. These advances may reduce treatment-related morbidity, improve durability of remission, and support a more personalized approach to clinical care and translational research in AAV.
2026-03-16 | Anti CD19 targeting CAR T cell therapy in ANCA-associated vasculitis.
To present a successful case study of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a patient with relapsing granulomatosis with polyangiitis (GPA). A 69-year-old male patient suffering from relapsing GPA refractory to standardized immunosuppression underwent an experimental therapy involving CD19-targeting CAR T cells. The conditioning regimen consisted of fludarabine and cyclophosphamide. Follow-up intervals scheduled at 1 to 3 months' intervals, incorporated evaluations of the BVAS, CT scans of the lungs, CRP, peripheral white blood cell count (WBC), lactate dehydrogenase, ANCA, immunoglobulin levels, post-CAR T-cell treatment surveillance including (CAR)-lymphocyte counts. The patient was diagnosed with GPA involving the lungs in 2019. He showed a relapsed refractory disease course in spite of treatment with rituximab, cyclophosphamide, avacopan, azathioprine, leflunomide and prednisolone. At presentation for CAR T-cell treatment, the BVAS was 14, inflammation markers were elevated, and pulmonary infiltrates were visible on the CT scan. CAR T-cell therapy was well-tolerated with no cytokine release syndrome (CRS) or neurotoxicity, and led to rapid improvement of clinical condition, as well as radiological and laboratory test results. CAR T cells expanded with a transient peak but were not anymore detectable in the peripheral blood around day 90. In line the significant B-cell depletion and hypogammaglobulinemia observed post-treatment showed gradual recovery. At the latest follow-up of 12-months post-treatment, the patient is in complete remission without further medication. CD19-targeted CAR T-cell therapy was safe and efficacious in a patient with relapsed and refractory GPA. CAR T-cell therapy has the potential to transform disease management and improve long-term outcomes for affected patients.
2025-12-31 | Plasma Exchange as an Adjunctive Therapeutic Option for Severe and Refractory Antineutrophil Cytoplasmic Antibody-Negative Microscopic Polyangiitis and Granulomatosis with Polyangiitis.
Background and Objectives: This study investigated and compared the efficacy of therapeutic plasma exchange (PEX) between antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) presenting with diffuse alveolar haemorrhage (DAH) and rapidly progressive glomerulonephritis (RPGN). Materials and Methods: A total of 336 patients with ANCA-associated vasculitis were screened, and 34 patients with MPA/GPA receiving PEX for DAH or RPGN were included. PEX was performed a total of 5-6 times consecutively (three times a week × 2 weeks) in all 34 patients. All-cause mortality (ACM) and end-stage kidney disease (ESKD) were evaluated as poor outcomes of MPA/GPA. Clinical data and poor outcomes were compared between ANCA-positive and ANCA-negative MPA/GPA patients receiving PEX. Results: The median age of the 34 MPA/GPA patients was 67 years (15 men and 19 women), of whom two were diagnosed with ANCA-negative vasculitis. Among the 34 patients, 28 (82.4%) received PEX owing to RPGN, and 6 (17.6%) due to DAH. During follow-up, 13 patients (38.2%) died, and 15 (44.1%) progressed to ESKD. Serum protein and C-reactive protein levels at AAV diagnosis were higher in ANCA-positive MPA/GPA patients than in ANCA-negative patients, although the difference was not statistically significant. Similarly, there were no differences in ACM or ESKD between the two groups during follow-up. Survival analysis showed that ANCA-positive MPA/GPA patients did not have significantly different cumulative patient or ESKD-free survival rates compared to ANCA-negative patients. Conclusions: This pilot study is the first to demonstrate the clinical feasibility of PEX in managing severe and refractory ANCA-negative MPA and GPA.
2025-12-06 | Circulating peripheral helper T cells are expanded and associate with disease activity in granulomatosis with polyangiitis.
Peripheral helper T (Tph) cells, a recently identified Th cell subset, have been implicated in various autoimmune diseases. However, their role in granulomatosis with polyangiitis (GPA) remains unclear. This study aimed to investigate the potential clinical significance of circulating Tph cells (cTph) in GPA. Peripheral blood mononuclear cells were collected from 74 remission GPA-patients, 26 active GPA-patients and 22 age- and sex-matched healthy controls. Flow cytometry was used to quantify cTph cells and their subset distribution. Single-cell multi-omics profiling was performed in an independent cohort (5 remission GPA-patients, 5 active GPA-patients and 5 healthy controls). Plasma IL-21 levels were measured by enzyme-linked immunosorbent assay, and associations between cTph cells and clinical parameters were evaluated. active GPA-patients showed an increased frequency and absolute number of cTph compared to remission GPA-patients, and both GPA groups exhibited cTph2-skewed distribution compared to healthy controls. Remission GPA-patients with generalized disease exhibited higher cTph frequencies than those with localized disease. cTph cells from active GPA-patients displayed an activated phenotype and a transcriptional profile marked by pro-inflammatory and survival-associated genes. Plasma IL-21 levels did not differ significantly between the three groups. Notably, absolute counts of memory cTph and cTph2 cells correlated positively with clinical markers of disease activity, and were significantly elevated in GPA patients with higher cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) titers. cTph cells are expanded and exhibit an activated, pro-inflammatory profile with a cTph2-skewed distribution in active GPA-patients. Their association with disease activity may support a potential role in disease pathogenesis and highlight their potential as therapeutic targets, warranting further investigation.
2025-08-02 | Pathologic Evidence of Granulomatosis With Polyangiitis as a Cause of Atrioventricular Block.
Atrioventricular block (AVB) is a rare manifestation of granulomatosis with polyangiitis (GPA), and the underlying pathologic relationship between GPA and AVB remains poorly understood. We present the case of a 71-year-old woman who developed complete AVB and had a history of microscopic polyangiitis. Despite the absence of clinical signs indicative of GPA relapse throughout her lifetime, postmortem examination revealed microgranulomas and multinucleated giant cells within the atrioventricular node. This case provides pathologic evidence that GPA can lead to complete heart block as an initial clinical manifestation. GPA-associated AVB can improve with immunosuppressive therapy. GPA should be considered in the differential diagnosis of AVB of unknown etiology.
antibodies
2026-08-08 | Eosinophilic granulomatosis with polyangiitis complicated by pulmonary aspergillosis and misdiagnosed as allergic bronchopulmonary aspergillosis: a case report.
To enhance the diagnostic and therapeutic awareness of eosinophilic granulomatosis with polyangiitis (EGPA) complicated by pulmonary aspergillosis. We report a case of EGPA initially misdiagnosed as allergic bronchopulmonary aspergillosis (ABPA) in a 52-year-old female patient. The patient presented with intermittent wheezing for more than six months and had a history of sinusitis. An outside hospital diagnosed ABPA based on pulmonary opacities, bronchiectasis, and evidence of Aspergillus infection, but standard therapy proved ineffective. Upon admission, laboratory findings revealed a markedly elevated absolute peripheral blood eosinophil count (5.29 × 109/L) and positivity for MPO-ANCA and p-ANCA. Serum total IgE was 8.85 IU/mL, and specific IgE to Aspergillus fumigatus was <0.10 IU/mL, both of which were inconsistent with ABPA. Chest CT showed multiple bilateral patchy and nodular opacities with bronchiectasis. Bronchoalveolar lavage fluid targeted next-generation sequencing (tNGS) detected Aspergillus at the genus level (23 sequence reads, relative abundance 33.39%). The diagnosis was revised to EGPA complicated by pulmonary aspergillosis. The patient was treated with glucocorticoids combined with mepolizumab, supplemented with voriconazole. Following treatment, the patient's symptoms resolved, with near normalization of imaging findings and pulmonary function. After 10 months of follow-up, methylprednisolone was completely discontinued in December 2025, and at the last follow-up in May 2026, the patient had been off glucocorticoids for 5 months, with sustained remission and successful extension of the mepolizumab dosing interval to 8 weeks. For patients presenting with refractory asthma accompanied by eosinophilia and pulmonary opacities, EGPA should be highly suspected. Glucocorticoids combined with mepolizumab is effective. In patients achieving sustained remission, extending the mepolizumab dosing interval to 8 weeks may be a safe and effective long-term maintenance strategy in carefully selected patients, though this observation requires further validation in prospective studies.
2026-08-05 | Antineutrophil cytoplasmic antibody-positive giant cell arteritis: Small-vessel vasculitis mimicking large-vessel vasculitis.
Giant cell arteritis is the most common vasculitis in those over 50 years old with a peak incidence between 70 and 80. Symptoms include a new-onset headache, scalp tenderness, jaw/tongue claudication, and visual symptoms, which can be sight-threatening. We report a case of an 82-year-old lady who presented with typical symptoms of giant cell arteritis and bilateral halo sign on an ultrasound scan. Despite initial steroid treatment she deteriorated and developed neurological symptoms including mononeuritis multiplex. Following further investigations, it was found that she was suffering from granulomatosis with polyangiitis and treatment was adjusted accordingly with additional immunomodulating treatment preventing further progression of symptoms. This case highlights how granulomatosis with polyangiitis can mimic giant cell arteritis and should be considered in refractory cases.
2026-08-04 | Exploring pathogenetic mechanisms in subglottic stenosis: A narrative review toward an integrated molecular classification.
Subglottic stenosis (SGS) is a chronic fibroinflammatory condition that causes pathological narrowing of the airway between the vocal cords and the trachea, with symptoms ranging from dyspnea to stridor and respiratory failure. The causes are heterogeneous: traumatic iatrogenic forms (such as prolonged intubation), autoimmune (e.g., granulomatosis with polyangiitis), post-viral (including COATS related to COVID-19), and idiopathic (iSGS), the latter affecting primarily adult Caucasian women with no obvious predisposing factors. All forms share a common pathogenetic core: epithelial damage, immune activation, chronic inflammation, and progressive fibrosis. Recent molecular studies, however, reveal that different variants of SGS exhibit distinct biological signatures, suggesting the existence of molecular subtypes with differentiated clinical courses. The emerging approach therefore aims for a biomarker-based classification for precision medicine. Future treatments may include targeted immunotherapies (e.g., IL-17A/IL-23 inhibitors), anti-fibrotic drugs, and epithelial regeneration strategies, alongside current surgical techniques to improve long-term prognosis.
2026-08-03 | Recurrent Multi-level Spinal Subdural Hematoma in Granulomatosis with Polyangiitis: A Therapeutic Dilemma Between Ischemia and Hemorrhage.
Spinal subdural hematoma (SSDH) associated with granulomatosis with polyangiitis (GPA) is extremely rare. A 63-year-old man with GPA and recurrent cerebral infarctions developed multi-level SSDHs while receiving immunotherapy and antithrombotic therapy. The hematomas were resolved conservatively, but they recurred in the posterior fossa and thoracic spine one year later. High cerebrospinal fluid interleukin-6 levels during ischemic events suggest active central nervous system vasculitis. This case illustrates a critical therapeutic dilemma: managing the competing risks of vasculitic ischemic stroke and hemorrhagic complications, such as SSDH. This case highlights the importance of balancing aggressive immunotherapy to suppress the vasculitis activity with cautious antithrombotic management.
2026-07-31 | Biosimilar Rituximab in ANCA-Associated Vasculitis Compared to the Originator: A Multicenter Cohort Study.
To evaluate the six-month effectiveness and safety of rituximab biosimilars compared to the originator in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and outcomes following originator to biosimilar switching. We recruited adults with GPA or MPA treated with the rituximab originator or a biosimilar for induction or maintenance, or who switched from originator to biosimilar maintenance (2018-2023). Participants either started the treatment within the preceding six months or were recruited from vasculitis research cohorts. Outcomes included six-month remission (Birmingham Vasculitis Activity Score [BVAS] version 3 of 0), relapse (BVAS rise after achieving remission requiring treatment), vasculitis damage, and serious adverse events (SAEs). We studied 207 participants from 9 centers: 132 starting induction (58 originator and 74 biosimilar), 59 starting maintenance (23 originator and 36 biosimilar), and 16 in the "switch" group. Mean age was 56.7 years (SD 17.5), 52% were female, 80% were White, and 70% had GPA. At six months from induction, 51 of 53 (96%) originator and 66 of 73 (90%) biosimilar recipients achieved remission (difference 6%, 95% confidence interval [CI] -4% to 15%), whereas at three months (exploratory) 48 of 51 (94%) and 57 of 72 (79%) recipients, respectively, had achieved remission (difference 15%, 95% CI 2% to 26%). All individuals in the maintenance and "switch" subgroups were in remission at six months. One minor relapse occurred in each of the induction groups and in the originator maintenance group. Change in vasculitis damage and SAEs were not significantly different between groups. This study found no significant differences in six-month outcomes between the rituximab originator and biosimilars for induction of GPA and MPA, with no concerning early signals in those initiating maintenance or switching from the originator to a biosimilar.
proteins
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.
2026-02-18 | Structures of proteinase 3 and the CD177 receptor complex reveal a major autoantibody epitope.
Granulomatosis with polyangiitis is a life-threatening systemic vasculitis, characterised by anti-neutrophil cytoplasmic autoantibodies (ANCA) most commonly against proteinase 3 (PR3), a protease expressed intracellularly and on the surface of neutrophils. Most cell surface PR3 is bound to the receptor CD177; however, the molecular mechanism of the interactions is not well understood. Here, we present crystal structures of CD177 in complex with PR3 and unliganded CD177. We describe a mainly hydrophobic binding interface between PR3 and CD177, involving the first two Ly6/uPAR (LU) domains of CD177. These form a globular structure which is connected to downstream domains via a flexible linker. Using a panel of PR3-ANCA-positive patient samples, we show that a significant proportion of ANCAs target the CD177-binding site of PR3 in these samples. Structure-guided mutation of the CD177-binding site on PR3 is effective in reducing PR3-ANCA binding. The results demonstrate that the CD177-binding surface of PR3 harbours a major PR3-ANCA epitope, and that the extent of binding to this surface varies between different patients.
2026-01-05 | Similar and yet not quite the same: unmasking distinct type I interferon signatures in ANCA vasculitis.
Antineutrophil cytoplasmic autoantibody-associated vasculitides can be classified by clinical phenotype or antineutrophil cytoplasmic autoantibody specificity, with overlapping yet distinct characteristics. Transcriptomic analyses of kidney biopsies from 2 French antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) cohorts revealed a pronounced type I interferon signature in microscopic polyangiitis (microscopic polyangiitis/myeloperoxidase-AAV) compared with granulomatosis with polyangiitis (granulomatosis with polyangiitis/proteinase 3-AAV). Among biopsies with high interferon scores, 66% were myeloperoxidase-AAV and 28% proteinase 3-AAV. The interferon score was associated with decreased kidney survival. These findings highlight AAV patient heterogeneity and support targeted treatment approaches.
2024-08-11 | Dynamics of scFv-targeted VAP2 correlating with IL-16, MIF and IL-1Ra in ANCA-associated vasculitis.
Using a mouse model of MPA with microvascular lesion with a clone (VasSF) of recombinant single chain fragments of the variable region of human IgG, we previously showed that vasculitis-associated apolipoprotein A2 (VAP2) may be a therapeutic target for vasculitis. The present study estimated the target molecules for VasSF and the association between VAP2 and cytokine levels in patient sera in terms of microvascular lesion severity. Sera and clinical information were collected from patients with microscopic polyangiitis and granulomatosis with polyangiitis (MPA/GPA) and infectious disease. Neutrophil counts, levels of C-reactive protein (CRP), creatinine, total cholesterol associated with microvascular lesion, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, glomerular filtration rate (eGFR), and cytokines were estimated. Serum VAP2 signals were determined with Western blotting. VasSF bound to a 24 kDa molecule in the serum of active MPA/GPA patients. Anti-AP2 antibody also bound with the same 24 kDa molecule, named VAP2, because of size difference from normal APOA2. The VAP2 signal was significantly stronger in the active-disease group but significantly weakened in remission. The signal correlated positively with eGFR but not with the Birmingham Vasculitis Activity Score, CRP, MPO-ANCA, or PR3-ANCA levels. It correlated negatively with MPO activity, IL-16, MIF, and IL-1Ra. Moreover, VasSF bound to a 17 kDa molecule in the remission phase. The 24 kDa VAP2 molecule may be associated with neutrophil functions because of its inverse correlation with MPO activity, IL-16, MIF, and IL-1Ra, suggesting that VAP2-APOA1 formation in HDL triggers microvascular injury. VasSF may reverse the injury by removing APOA1-VAP2 heterodimers from peripheral blood vessels.
2023-04-22 | Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with granulomatosis with polyangiitis
Abstract Objectives Granulomatosis with polyangiitis (GPA) is a chronic relapsing systemic autoimmune vasculitis. Current treatment of GPA is unsatisfactory, as it relies on strong immunosuppressive regimens, with either CYC or rituximab, which reduce the immunogenicity of several vaccines and are risk factors for a severe form of COVID-19. This emphasizes the need to identify new drug targets and to develop treatment strategies with less harmful side effects. Since CD4+ effector memory T cells (TEM) play a key role in the pathogenesis of GPA, we aimed in this study to modulate CD4+TEM cell activity via Kv1.3 blockade using the specific peptide inhibiter, ShK-186. Methods Peripheral blood samples from 27 patients with GPA in remission and 16 age- and sex-matched healthy controls (HCs) were pre-incubated in vitro in the presence or absence of ShK-186, followed by stimulation with phorbol myristate acetate, calcium ionophore and brefeldin-A. The effect of ShK-186 on the cytokine production (IFNγ, TNFα, IL-4, IL-17, IL-21) within total and subsets of CD4+ T helper (CD4+TH) cells were assessed using flow cytometry. Results ShK-186 reduced the expression level of IFNγ, TNFα, IL-4, IL-17 and IL-21 in CD4+TH cells from patients with GPA in vitro. Further analysis performed on sorted CD4+T cell subsets, revealed that ShK-186 predominantly inhibited the cytokine production of CD4+TEM cells. ShK-186 treatment reduced the production of the pro-inflammatory cytokines to the level seen in CD4+ TH cells from HCs. Conclusions Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects.
other
2025-10-24 | Granulomatous Reactions Following the Injection of Multiple Aesthetic Microimplants: A Complication Associated with Excessive Filler Exposure in a Predisposed Patient.
Background and Clinical Significance: Granulomatous reactions are rare but clinically significant complications of aesthetic procedures involving dermal fillers, particularly in individuals with underlying immune dysregulation. These reactions present diagnostic and therapeutic challenges, especially when associated with undiagnosed or latent autoimmune diseases. This case illustrates the interaction between filler composition, immune status, and the risk of delayed inflammatory responses, underscoring the need for thorough patient evaluation and individualized management strategies. Case Presentation: A 49-year-old woman developed delayed-onset subcutaneous nodules following midface augmentation with two filler types: a monophasic, cross-linked hyaluronic acid gel (concentration 20 mg/mL, 1.0 mL per side) injected into the deep malar fat pads, and a calcium hydroxyapatite suspension (30% CaHA microspheres in a carboxymethylcellulose carrier, 0.5 mL per side) placed in the subdermal plane along the zygomatic arch. The procedure was performed in a single session using a 22 G blunt cannula, with no immediate adverse events. High-resolution ultrasound demonstrated hypoechoic inflammatory nodules without systemic symptoms. A retrospective review of her medical history revealed a latent, previously undisclosed diagnosis of granulomatosis with polyangiitis (GPA). The immune-adjuvant properties of calcium hydroxyapatite likely triggered a localized pro-inflammatory response in this predisposed patient. A conservative, staged, non-invasive therapeutic protocol-saline infiltration, intradermal polynucleotide injections, and manual lymphatic drainage-achieved complete clinical and radiological resolution without systemic immunosuppression or surgical intervention. Conclusions: This case highlights the critical importance of pre-procedural immunological assessment in aesthetic medicine. Subclinical autoimmune conditions may predispose patients to delayed granulomatous reactions after filler injections. An individualized, conservative management strategy can effectively resolve such complications while minimizing the risks associated with aggressive treatment. Greater awareness of immune-mediated responses to dermal fillers is essential to ensure patient safety and optimize clinical outcomes.
2023-08-21 | BA.1/BA.5 Immunogenicity, Reactogenicity, and Disease Activity after COVID-19 Vaccination in Patients with ANCA-Associated Vasculitis: A Prospective Observational Cohort Study
Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited data on SARS-CoV-2 vaccination and prospective studies that have focused exclusively on AAV patients are lacking. In addition, there are safety concerns regarding the use of highly immunogenic mRNA vaccines in autoimmune diseases, and further studies investigating reactogenicity are urgently needed. In this prospective observational cohort study, we performed a detailed characterization of neutralizing antibody responses against omicron subtypes and provided a longitudinal assessment of vaccine reactogenicity and AAV disease activity. Different vaccine doses were generally well tolerated and no AAV relapses occurred during follow-up. AAV patients had significantly lower anti-S1 IgG and surrogate-neutralizing antibodies after first, second, and third vaccine doses as compared to healthy controls, respectively. Live-virus neutralization assays against omicron subtypes BA.1 and BA.5 revealed that previous SARS-CoV-2 vaccines result in an inadequate neutralizing immune response in immunocompromised AAV patients. These data demonstrate that new vaccination strategies including adapted mRNA vaccines against epitopes of emerging variants are needed to help protect highly vulnerable individuals such as AAV patients.
2022-12-01 | Herpes zoster infection after rituximab induction therapy in patient with myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis: a case report
Induction treatment with rituximab-an anti-CD20 monoclonal antibody-may increase the risk of varicella-zoster virus (VZV) reactivation in patients with antineutrophil-cytoplasmic-antibody-associated vasculitis (AAV). Our case report shows VZV reactivation following rituximab treatment in AAV patients. The recombinant zoster vaccine should be recommended before the start of induction treatment with rituximab.
2020-02-22 | Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients
Abstract Objective To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls. Methods Patients receiving rituximab ( n = 30), abatacept ( n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls ( n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 μg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F. Results Compared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls ( p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group ( p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs ( p = 0.03) and controls ( p = 0.001). Rituximab treatment was associated with large reduction (coefficient − 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients − 1.9 and − 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls. Conclusions Prime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab. Trial registration ClinicalTrials.gov , NCT03762824 . Registered on 4 December 2018, retrospectively registered
2013-06-01 | THU0306 Cellular and Humoral Responses to Varicella-Zoster Virus in Patients with Autoimmune Diseases
Herpes zoster (HZ) results from reactivation of varicella-zoster virus (VZV). Besides the symptoms of HZ, 8-27% of patients with herpes zoster develop postherpetic neuralgia (PHN), leading to debilitating pains. In particular elderly, HIV-patients and patients using immunosuppressive drugs are at increased risk for developing HZ and PHN. Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA) have a 5 to 16-fold increased risk compared to the general population. Use of immunosuppressive drugs is associated with the development of HZ in these patients. Aim of the study was to evaluate if the susceptibility of patients with autoimmune disease is due to decreased levels of cellular and/or humoral responses to VZV in these patients. A cross-sectional study on VZV-specific immunity was performed in 78 patients with SLE, 71 patients with GPA and 65 age- and sex-matched healthy controls (HC). In all individuals, serum antibody levels to VZV-glycoprotein (Gp) was measured by an in-house ELISA and, in a large proportion of tested individuals, compared to responses measured by VIDAS and Serion VZV-Gp ELISA. As control antibodies to Diphtheria (IBL-International) were measured in all participants. Cellular responses to VZV were measured in a large proportion of patients and controls by IFN-γ ELIspot assay and CFSE-dye dilution proliferation assay using cryopreserved PBMCs and UV-inactivated VZV as antigen. There was a strong correlation between the values measured with the in-house anti-Gp-VZV ELISA and VIDAS, and Serion anti-Gp-VZV ELISA (all p<0.0001). Antibodies to VZV were significantly (P=0.0005) increased in SLE patients (median 2019 mIU/ml, range 210 - ≥10000) compared to HC (median 1110 mIU/ml, range 110 - 8224). Values in GPA patients (median 1495 mIU/ml, range 20 - ≥10000) were not statistically different from values in HC. In contrast, antibodies against Diphtheria in both SLE and GPA patients were significantly (P<0.001) decreased compared to HC. Moreover, SLE and GPA patients had a significantly lower number of IFN-γ spot forming cells against VZV (P<0.05). Furthermore, the proliferation index (PI) of CD4+ T-lymphocytes was significantly (P<0,05) decreased in SLE patients compared to HC, but not in GPA patients. Patients with SLE have increased antibody levels against VZV compared to levels detected in HC, which cannot be explained by polyclonal hypergammaglobulinaemia as antibodies to Diphtheria were decreased in comparison to HC. Cellular immunity however, was decreased in these patients as well as in GPA patients. Our results suggest that increased prevalence of VZV in SLE and GPA patients is due to a poor cellular response to VZV. Vaccination strategies should not be based upon humoral immunity and should aim to boost cellular immunity against VZV. None Declared
small molecules
2026-08-07 | Hepatic granulomas as a manifestation of ANCA-associated vasculitis:a systematic review.
ANCA-associated vasculitides (AAV) - granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) - are rare small-vessel autoimmune diseases. Liver involvement in AAV is uncommon and generally manifests as biochemical hepatitis; true hepatic granulomatosis is exceedingly rare and diagnostically challenging. We conducted a systematic scoping review following PRISMA-ScR guidelines and the Arksey & O'Malley framework, searching PubMed, Google Scholar, ScienceDirect, and Scopus without date restriction (through March 2026). A total of 7, 033 records were initially retrieved; after deduplication, title/abstract screening, and full-text review, five articles meeting strict inclusion criteria were included for qualitative synthesis. Five published cases of hepatic granulomas in AAV patients with no confirmed confounding etiology were identified. All were GPA or EGPA; no case of pure MPA was documented. Three patients were female and two were male, with a mean age of 57.6 years. Liver histology revealed non-necrotizing epithelioid granulomas (n = 2), granulomatous inflammation with necrosis (n = 1), incomplete septal cirrhosis with vasculopathic changes (n = 1), and incidental calcified granulomas (n = 1). Immunosuppressive therapy with corticosteroids and/or cyclophosphamide achieved clinical and biochemical improvement in all treated patients. Hepatic granulomatosis is a rare but genuine extra-respiratory manifestation of AAV, most frequently reported in GPA. It may antedate the canonical ENT-pulmonary-renal triad, presenting as incidental hepatomegaly or unexplained liver function test elevation. Systematic exclusion of competing etiologies (sarcoidosis, tuberculosis, primary biliary cholangitis, drug-induced hepatitis) is mandatory before attributing granulomas to AAV. Liver biopsy remains pivotal in confirming the diagnosis. Immunosuppression is the therapeutic cornerstone, with generally favourable outcomes.
2026-08-05 | Anterior ischaemic optic neuropathy as an initial manifestation of eosinophilic granulomatosis with polyangiitis: The importance of early and appropriate immunosuppressive treatment for visual recovery.
Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody-associated vasculitis, affecting various organs. Although ocular involvement occurred in 6.8-11.1% of patients, anterior ischaemic optic neuropathy (AION) is rare. We present the case of a 57-year-old woman with an 11-year history of asthma who developed sudden, painless visual loss in her left eye. On admission (3 days after symptom onset), visual acuity was counting fingers in the left eye and 20/20 in the right eye. Funduscopy showed left optic disc oedema. Magnetic resonance imaging revealed intravitreal protrusion of the left optic nerve head with restricted diffusion and local contrast enhancement of the left intraorbital and retrobulbar fat. Given also peripheral eosinophilia, myeloperoxidase-antineutrophil cytoplasmic antibody positivity, mononeuritis multiplex, nasal polyps, sinusitis, and pulmonary involvement, EGPA with AION was diagnosed. Intravenous methylprednisolone pulse was urgently administered, followed by mepolizumab 2 weeks later. Although eosinophilic inflammation and imaging findings improved, visual acuity remained unchanged over 1 year. A literature review identified 14 cases of EGPA-associated AION. Including our case, 11 cases with available data (14 eyes) were analysed. Overall, visual recovery was observed in 29%. Among 12 eyes with severe visual impairment before treatment, visual recovery occurred only in those treated earlier or with cyclophosphamide except for one, whereas no recovery occurred in those with delayed treatment or without cyclophosphamide. This case highlights the potential of AION as an initial manifestation of EGPA. Both earlier initiation and adequate intensity of immunosuppressive therapy, particularly including cyclophosphamide when clinically appropriate, may be important for visual recovery in EGPA-associated severe AION.
2026-07-28 | Advances in the Diagnosis, Treatment and Prognosis of ANCA-Associated Glomerulonephritis.
ANCA-associated vasculitis (AAV) with kidney involvement represents small-vessel vasculitis, characterized by rapidly progressive glomerulonephritis and a high risk of end-stage kidney disease (ESKD) and increased mortality. AAV typically presents with multisystem involvement, with renal manifestations occurring more frequently in microscopic polyangiitis (MPA) (90-100%) and granulomatosis with polyangiitis (GPA) (50-80%). The classic clinical presentation includes acute kidney injury with hematuria and proteinuria, accompanied by ANCA positivity (MPO-ANCA or PR3-ANCA). Histologically, the predominant pattern is segmental necrotizing glomerulonephritis with crescent formation. Treatment consists of two phases: (a) induction of remission with a lower cumulative dose of glucocorticoids (according to the reduced-dose PEXIVAS regimen) in combination with rituximab or cyclophosphamide and (b) maintenance of remission with rituximab for 2-4 years. The C5a receptor inhibitor avacopan can be used as a steroid-sparing agent in patients with severe kidney involvement or at high risk of corticosteroid-related complications. Beyond the traditional markers of disease activity (hematuria, proteinuria, eGFR), novel biomarkers such as urinary soluble CD163, MCP-1, complement activation products (C5a, sC5b-9), and urinary Treg/Th17 profiles have demonstrated prognostic value. Early diagnosis and prompt initiation of immunosuppressive therapy significantly improve both kidney and overall survival, while prevention of relapses and long-term complications plays a key role in improving the long-term prognosis of patients with AAV.
2026-06-25 | No benefit of adding glucocorticoids to maintenance treatment in reducing the risk of major relapses in ANCA-associated vasculitis: real life data from a longitudinal cohort study.
To examine the role of low-dose glucocorticoids (GCs) in major relapse, hospitalisation and damage accumulation risk during maintenance therapy in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs). Retrospective cohort study of newly diagnosed patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) followed in three tertiary referral centres. We recorded relapses (Birmingham Vasculitis Activity Score increase >0), increases in Vasculitis Damage Index (VDI) and hospitalisations. We used time-varying and mixed-effects Cox models to examine the effect of GCs on the risk of major relapses, VDI accumulation and hospitalisations. Sensitivity analysis was also conducted to address potential confounding. 171 patients (GPA: 107, MPA: 64, median age: 61 years) were included with a median follow-up of 88.2 months (803.4 patient years (PY)). We recorded 65 major relapses (8.1/100 PY) in 48 patients (28%), 65 events of new damage (8.1/100 PY) and 132 hospitalisations (16.4/100 PY). By multivariable analysis, rituximab use was associated with a lower risk (HR=0.21, 95% CI 0.09 to 0.47, p=0.0001) while disease activity at diagnosis was associated with an increased risk (HR=1.17, 95% CI 1.03 to 1.33, p=0.013) of major relapses. Low-dose GCs were not associated with a reduced major relapse risk (HR=0.96, 95% CI 0.88 to 1.05, p=0.36) but they were associated with a risk of damage accumulation (HR=1.52, 95% CI 1.19 to 1.93, p=0.0007) and hospitalisations (HR=1.24, 95% CI 1.06 to 1.45, p=0.006). Higher GC exposure during maintenance therapy was not significantly associated with a lower major relapse risk whereas it was associated with damage accrual and hospitalisation. These findings may support decision making regarding long-term GC use in patients with GPA/MPA.
2026-06-05 | Early relapse under the LoVAS reduced-dose glucocorticoid regimen in ANCA-associated vasculitis: a single-center retrospective observational study.
To evaluate early relapse and other clinical outcomes in patients with microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) treated with reduced-dose glucocorticoid (GC) regimens, with a focus on the LoVAS regimen in comparison with the PEXIVAS regimen. We conducted a retrospective single-center cohort study of consecutive patients with newly diagnosed or relapsing MPA or GPA treated between March 2022 and September 2025. Patients were classified into LoVAS or PEXIVAS groups if they adhered to the assigned reduced-dose GC regimens for at least 14 days. The primary outcome was time to first relapse. Secondary outcomes included time to GC withdrawal, time to serious adverse events, and cumulative GC exposure. Time-to-event outcomes were analyzed descriptively using Kaplan-Meier curves and log-rank tests and were interpreted as exploratory because of the small sample size and limited number of events. A total of 21 patients were included (LoVAS, n = 5; PEXIVAS, n = 16). Relapse occurred in 3/5 patients in the LoVAS group and 2/16 patients in the PEXIVAS group. In the LoVAS group, relapses occurred on days 21, 52, and 128 after treatment initiation. GC was withdrawn in 5/5 patients in the LoVAS group and 5/16 patients in the PEXIVAS group. Serious adverse events occurred in 3/5 patients in the LoVAS group and 7/16 patients in the PEXIVAS group. The median average daily prednisolone-equivalent dose was lower in the LoVAS group than in the PEXIVAS group: 3.06 mg/day versus 14.5 mg/day. These findings were interpreted descriptively because of the small sample size and limited number of events. These findings should be interpreted as hypothesis-generating and suggest that early relapse may occur in some patients treated with the LoVAS regimen in real-world practice. Further studies with larger cohorts and appropriate adjustment for confounding factors are needed.
cell therapies
2026-05-14 | ANCA vasculitis: what is in the pipeline.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is now recognized as a complex immune-mediated inflammatory disorder rather than a purely pauci-immune small-vessel vasculitis. Advances in understanding ANCA specificity, complement activation, neutrophil extracellular trap formation, genetic susceptibility, and environmental triggers have reshaped concepts of disease classification, prognosis, and therapy. A focused review of these developments is timely because they are directly informing current treatment strategies, disease stratification, and future drug development. Treatment has shifted from conventional cyclophosphamide and glucocorticoids toward targeted, steroid-sparing approaches. Rituximab is now central to remission induction and maintenance, while avacopan in GPA (granulomatosis with polyangiitis) and MPA (microscopic polyangiitis) and interleukin (IL)-5 blockade in EGPA (eosinophilic granulomatosis with polyangiitis) further reduce glucocorticoid exposure and toxicity. Emerging therapies include next-generation anti-CD20 monoclonal antibodies such as obinutuzumab, CAR-T cell strategies, and other precision immunologic approaches targeting B-cell pathways, including BAFF/APRIL blockade, tyrosine kinase inhibitors (TKIs) and complement-directed therapies designed to more selectively interrupt pathogenic inflammation. Improved biologic insight is enabling biomarker-driven classification and mechanism-based therapy selection. These advances may reduce treatment-related morbidity, improve durability of remission, and support a more personalized approach to clinical care and translational research in AAV.
2026-03-16 | Anti CD19 targeting CAR T cell therapy in ANCA-associated vasculitis.
To present a successful case study of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a patient with relapsing granulomatosis with polyangiitis (GPA). A 69-year-old male patient suffering from relapsing GPA refractory to standardized immunosuppression underwent an experimental therapy involving CD19-targeting CAR T cells. The conditioning regimen consisted of fludarabine and cyclophosphamide. Follow-up intervals scheduled at 1 to 3 months' intervals, incorporated evaluations of the BVAS, CT scans of the lungs, CRP, peripheral white blood cell count (WBC), lactate dehydrogenase, ANCA, immunoglobulin levels, post-CAR T-cell treatment surveillance including (CAR)-lymphocyte counts. The patient was diagnosed with GPA involving the lungs in 2019. He showed a relapsed refractory disease course in spite of treatment with rituximab, cyclophosphamide, avacopan, azathioprine, leflunomide and prednisolone. At presentation for CAR T-cell treatment, the BVAS was 14, inflammation markers were elevated, and pulmonary infiltrates were visible on the CT scan. CAR T-cell therapy was well-tolerated with no cytokine release syndrome (CRS) or neurotoxicity, and led to rapid improvement of clinical condition, as well as radiological and laboratory test results. CAR T cells expanded with a transient peak but were not anymore detectable in the peripheral blood around day 90. In line the significant B-cell depletion and hypogammaglobulinemia observed post-treatment showed gradual recovery. At the latest follow-up of 12-months post-treatment, the patient is in complete remission without further medication. CD19-targeted CAR T-cell therapy was safe and efficacious in a patient with relapsed and refractory GPA. CAR T-cell therapy has the potential to transform disease management and improve long-term outcomes for affected patients.
2025-12-31 | Plasma Exchange as an Adjunctive Therapeutic Option for Severe and Refractory Antineutrophil Cytoplasmic Antibody-Negative Microscopic Polyangiitis and Granulomatosis with Polyangiitis.
Background and Objectives: This study investigated and compared the efficacy of therapeutic plasma exchange (PEX) between antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) presenting with diffuse alveolar haemorrhage (DAH) and rapidly progressive glomerulonephritis (RPGN). Materials and Methods: A total of 336 patients with ANCA-associated vasculitis were screened, and 34 patients with MPA/GPA receiving PEX for DAH or RPGN were included. PEX was performed a total of 5-6 times consecutively (three times a week × 2 weeks) in all 34 patients. All-cause mortality (ACM) and end-stage kidney disease (ESKD) were evaluated as poor outcomes of MPA/GPA. Clinical data and poor outcomes were compared between ANCA-positive and ANCA-negative MPA/GPA patients receiving PEX. Results: The median age of the 34 MPA/GPA patients was 67 years (15 men and 19 women), of whom two were diagnosed with ANCA-negative vasculitis. Among the 34 patients, 28 (82.4%) received PEX owing to RPGN, and 6 (17.6%) due to DAH. During follow-up, 13 patients (38.2%) died, and 15 (44.1%) progressed to ESKD. Serum protein and C-reactive protein levels at AAV diagnosis were higher in ANCA-positive MPA/GPA patients than in ANCA-negative patients, although the difference was not statistically significant. Similarly, there were no differences in ACM or ESKD between the two groups during follow-up. Survival analysis showed that ANCA-positive MPA/GPA patients did not have significantly different cumulative patient or ESKD-free survival rates compared to ANCA-negative patients. Conclusions: This pilot study is the first to demonstrate the clinical feasibility of PEX in managing severe and refractory ANCA-negative MPA and GPA.
2025-12-06 | Circulating peripheral helper T cells are expanded and associate with disease activity in granulomatosis with polyangiitis.
Peripheral helper T (Tph) cells, a recently identified Th cell subset, have been implicated in various autoimmune diseases. However, their role in granulomatosis with polyangiitis (GPA) remains unclear. This study aimed to investigate the potential clinical significance of circulating Tph cells (cTph) in GPA. Peripheral blood mononuclear cells were collected from 74 remission GPA-patients, 26 active GPA-patients and 22 age- and sex-matched healthy controls. Flow cytometry was used to quantify cTph cells and their subset distribution. Single-cell multi-omics profiling was performed in an independent cohort (5 remission GPA-patients, 5 active GPA-patients and 5 healthy controls). Plasma IL-21 levels were measured by enzyme-linked immunosorbent assay, and associations between cTph cells and clinical parameters were evaluated. active GPA-patients showed an increased frequency and absolute number of cTph compared to remission GPA-patients, and both GPA groups exhibited cTph2-skewed distribution compared to healthy controls. Remission GPA-patients with generalized disease exhibited higher cTph frequencies than those with localized disease. cTph cells from active GPA-patients displayed an activated phenotype and a transcriptional profile marked by pro-inflammatory and survival-associated genes. Plasma IL-21 levels did not differ significantly between the three groups. Notably, absolute counts of memory cTph and cTph2 cells correlated positively with clinical markers of disease activity, and were significantly elevated in GPA patients with higher cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) titers. cTph cells are expanded and exhibit an activated, pro-inflammatory profile with a cTph2-skewed distribution in active GPA-patients. Their association with disease activity may support a potential role in disease pathogenesis and highlight their potential as therapeutic targets, warranting further investigation.
2025-08-02 | Pathologic Evidence of Granulomatosis With Polyangiitis as a Cause of Atrioventricular Block.
Atrioventricular block (AVB) is a rare manifestation of granulomatosis with polyangiitis (GPA), and the underlying pathologic relationship between GPA and AVB remains poorly understood. We present the case of a 71-year-old woman who developed complete AVB and had a history of microscopic polyangiitis. Despite the absence of clinical signs indicative of GPA relapse throughout her lifetime, postmortem examination revealed microgranulomas and multinucleated giant cells within the atrioventricular node. This case provides pathologic evidence that GPA can lead to complete heart block as an initial clinical manifestation. GPA-associated AVB can improve with immunosuppressive therapy. GPA should be considered in the differential diagnosis of AVB of unknown etiology.
antibodies
2026-08-08 | Eosinophilic granulomatosis with polyangiitis complicated by pulmonary aspergillosis and misdiagnosed as allergic bronchopulmonary aspergillosis: a case report.
To enhance the diagnostic and therapeutic awareness of eosinophilic granulomatosis with polyangiitis (EGPA) complicated by pulmonary aspergillosis. We report a case of EGPA initially misdiagnosed as allergic bronchopulmonary aspergillosis (ABPA) in a 52-year-old female patient. The patient presented with intermittent wheezing for more than six months and had a history of sinusitis. An outside hospital diagnosed ABPA based on pulmonary opacities, bronchiectasis, and evidence of Aspergillus infection, but standard therapy proved ineffective. Upon admission, laboratory findings revealed a markedly elevated absolute peripheral blood eosinophil count (5.29 × 109/L) and positivity for MPO-ANCA and p-ANCA. Serum total IgE was 8.85 IU/mL, and specific IgE to Aspergillus fumigatus was <0.10 IU/mL, both of which were inconsistent with ABPA. Chest CT showed multiple bilateral patchy and nodular opacities with bronchiectasis. Bronchoalveolar lavage fluid targeted next-generation sequencing (tNGS) detected Aspergillus at the genus level (23 sequence reads, relative abundance 33.39%). The diagnosis was revised to EGPA complicated by pulmonary aspergillosis. The patient was treated with glucocorticoids combined with mepolizumab, supplemented with voriconazole. Following treatment, the patient's symptoms resolved, with near normalization of imaging findings and pulmonary function. After 10 months of follow-up, methylprednisolone was completely discontinued in December 2025, and at the last follow-up in May 2026, the patient had been off glucocorticoids for 5 months, with sustained remission and successful extension of the mepolizumab dosing interval to 8 weeks. For patients presenting with refractory asthma accompanied by eosinophilia and pulmonary opacities, EGPA should be highly suspected. Glucocorticoids combined with mepolizumab is effective. In patients achieving sustained remission, extending the mepolizumab dosing interval to 8 weeks may be a safe and effective long-term maintenance strategy in carefully selected patients, though this observation requires further validation in prospective studies.
2026-08-05 | Antineutrophil cytoplasmic antibody-positive giant cell arteritis: Small-vessel vasculitis mimicking large-vessel vasculitis.
Giant cell arteritis is the most common vasculitis in those over 50 years old with a peak incidence between 70 and 80. Symptoms include a new-onset headache, scalp tenderness, jaw/tongue claudication, and visual symptoms, which can be sight-threatening. We report a case of an 82-year-old lady who presented with typical symptoms of giant cell arteritis and bilateral halo sign on an ultrasound scan. Despite initial steroid treatment she deteriorated and developed neurological symptoms including mononeuritis multiplex. Following further investigations, it was found that she was suffering from granulomatosis with polyangiitis and treatment was adjusted accordingly with additional immunomodulating treatment preventing further progression of symptoms. This case highlights how granulomatosis with polyangiitis can mimic giant cell arteritis and should be considered in refractory cases.
2026-08-04 | Exploring pathogenetic mechanisms in subglottic stenosis: A narrative review toward an integrated molecular classification.
Subglottic stenosis (SGS) is a chronic fibroinflammatory condition that causes pathological narrowing of the airway between the vocal cords and the trachea, with symptoms ranging from dyspnea to stridor and respiratory failure. The causes are heterogeneous: traumatic iatrogenic forms (such as prolonged intubation), autoimmune (e.g., granulomatosis with polyangiitis), post-viral (including COATS related to COVID-19), and idiopathic (iSGS), the latter affecting primarily adult Caucasian women with no obvious predisposing factors. All forms share a common pathogenetic core: epithelial damage, immune activation, chronic inflammation, and progressive fibrosis. Recent molecular studies, however, reveal that different variants of SGS exhibit distinct biological signatures, suggesting the existence of molecular subtypes with differentiated clinical courses. The emerging approach therefore aims for a biomarker-based classification for precision medicine. Future treatments may include targeted immunotherapies (e.g., IL-17A/IL-23 inhibitors), anti-fibrotic drugs, and epithelial regeneration strategies, alongside current surgical techniques to improve long-term prognosis.
2026-08-03 | Recurrent Multi-level Spinal Subdural Hematoma in Granulomatosis with Polyangiitis: A Therapeutic Dilemma Between Ischemia and Hemorrhage.
Spinal subdural hematoma (SSDH) associated with granulomatosis with polyangiitis (GPA) is extremely rare. A 63-year-old man with GPA and recurrent cerebral infarctions developed multi-level SSDHs while receiving immunotherapy and antithrombotic therapy. The hematomas were resolved conservatively, but they recurred in the posterior fossa and thoracic spine one year later. High cerebrospinal fluid interleukin-6 levels during ischemic events suggest active central nervous system vasculitis. This case illustrates a critical therapeutic dilemma: managing the competing risks of vasculitic ischemic stroke and hemorrhagic complications, such as SSDH. This case highlights the importance of balancing aggressive immunotherapy to suppress the vasculitis activity with cautious antithrombotic management.
2026-07-31 | Biosimilar Rituximab in ANCA-Associated Vasculitis Compared to the Originator: A Multicenter Cohort Study.
To evaluate the six-month effectiveness and safety of rituximab biosimilars compared to the originator in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and outcomes following originator to biosimilar switching. We recruited adults with GPA or MPA treated with the rituximab originator or a biosimilar for induction or maintenance, or who switched from originator to biosimilar maintenance (2018-2023). Participants either started the treatment within the preceding six months or were recruited from vasculitis research cohorts. Outcomes included six-month remission (Birmingham Vasculitis Activity Score [BVAS] version 3 of 0), relapse (BVAS rise after achieving remission requiring treatment), vasculitis damage, and serious adverse events (SAEs). We studied 207 participants from 9 centers: 132 starting induction (58 originator and 74 biosimilar), 59 starting maintenance (23 originator and 36 biosimilar), and 16 in the "switch" group. Mean age was 56.7 years (SD 17.5), 52% were female, 80% were White, and 70% had GPA. At six months from induction, 51 of 53 (96%) originator and 66 of 73 (90%) biosimilar recipients achieved remission (difference 6%, 95% confidence interval [CI] -4% to 15%), whereas at three months (exploratory) 48 of 51 (94%) and 57 of 72 (79%) recipients, respectively, had achieved remission (difference 15%, 95% CI 2% to 26%). All individuals in the maintenance and "switch" subgroups were in remission at six months. One minor relapse occurred in each of the induction groups and in the originator maintenance group. Change in vasculitis damage and SAEs were not significantly different between groups. This study found no significant differences in six-month outcomes between the rituximab originator and biosimilars for induction of GPA and MPA, with no concerning early signals in those initiating maintenance or switching from the originator to a biosimilar.
proteins
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.
2026-02-18 | Structures of proteinase 3 and the CD177 receptor complex reveal a major autoantibody epitope.
Granulomatosis with polyangiitis is a life-threatening systemic vasculitis, characterised by anti-neutrophil cytoplasmic autoantibodies (ANCA) most commonly against proteinase 3 (PR3), a protease expressed intracellularly and on the surface of neutrophils. Most cell surface PR3 is bound to the receptor CD177; however, the molecular mechanism of the interactions is not well understood. Here, we present crystal structures of CD177 in complex with PR3 and unliganded CD177. We describe a mainly hydrophobic binding interface between PR3 and CD177, involving the first two Ly6/uPAR (LU) domains of CD177. These form a globular structure which is connected to downstream domains via a flexible linker. Using a panel of PR3-ANCA-positive patient samples, we show that a significant proportion of ANCAs target the CD177-binding site of PR3 in these samples. Structure-guided mutation of the CD177-binding site on PR3 is effective in reducing PR3-ANCA binding. The results demonstrate that the CD177-binding surface of PR3 harbours a major PR3-ANCA epitope, and that the extent of binding to this surface varies between different patients.
2026-01-05 | Similar and yet not quite the same: unmasking distinct type I interferon signatures in ANCA vasculitis.
Antineutrophil cytoplasmic autoantibody-associated vasculitides can be classified by clinical phenotype or antineutrophil cytoplasmic autoantibody specificity, with overlapping yet distinct characteristics. Transcriptomic analyses of kidney biopsies from 2 French antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) cohorts revealed a pronounced type I interferon signature in microscopic polyangiitis (microscopic polyangiitis/myeloperoxidase-AAV) compared with granulomatosis with polyangiitis (granulomatosis with polyangiitis/proteinase 3-AAV). Among biopsies with high interferon scores, 66% were myeloperoxidase-AAV and 28% proteinase 3-AAV. The interferon score was associated with decreased kidney survival. These findings highlight AAV patient heterogeneity and support targeted treatment approaches.
2024-08-11 | Dynamics of scFv-targeted VAP2 correlating with IL-16, MIF and IL-1Ra in ANCA-associated vasculitis.
Using a mouse model of MPA with microvascular lesion with a clone (VasSF) of recombinant single chain fragments of the variable region of human IgG, we previously showed that vasculitis-associated apolipoprotein A2 (VAP2) may be a therapeutic target for vasculitis. The present study estimated the target molecules for VasSF and the association between VAP2 and cytokine levels in patient sera in terms of microvascular lesion severity. Sera and clinical information were collected from patients with microscopic polyangiitis and granulomatosis with polyangiitis (MPA/GPA) and infectious disease. Neutrophil counts, levels of C-reactive protein (CRP), creatinine, total cholesterol associated with microvascular lesion, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides, glomerular filtration rate (eGFR), and cytokines were estimated. Serum VAP2 signals were determined with Western blotting. VasSF bound to a 24 kDa molecule in the serum of active MPA/GPA patients. Anti-AP2 antibody also bound with the same 24 kDa molecule, named VAP2, because of size difference from normal APOA2. The VAP2 signal was significantly stronger in the active-disease group but significantly weakened in remission. The signal correlated positively with eGFR but not with the Birmingham Vasculitis Activity Score, CRP, MPO-ANCA, or PR3-ANCA levels. It correlated negatively with MPO activity, IL-16, MIF, and IL-1Ra. Moreover, VasSF bound to a 17 kDa molecule in the remission phase. The 24 kDa VAP2 molecule may be associated with neutrophil functions because of its inverse correlation with MPO activity, IL-16, MIF, and IL-1Ra, suggesting that VAP2-APOA1 formation in HDL triggers microvascular injury. VasSF may reverse the injury by removing APOA1-VAP2 heterodimers from peripheral blood vessels.
2023-04-22 | Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with granulomatosis with polyangiitis
Abstract Objectives Granulomatosis with polyangiitis (GPA) is a chronic relapsing systemic autoimmune vasculitis. Current treatment of GPA is unsatisfactory, as it relies on strong immunosuppressive regimens, with either CYC or rituximab, which reduce the immunogenicity of several vaccines and are risk factors for a severe form of COVID-19. This emphasizes the need to identify new drug targets and to develop treatment strategies with less harmful side effects. Since CD4+ effector memory T cells (TEM) play a key role in the pathogenesis of GPA, we aimed in this study to modulate CD4+TEM cell activity via Kv1.3 blockade using the specific peptide inhibiter, ShK-186. Methods Peripheral blood samples from 27 patients with GPA in remission and 16 age- and sex-matched healthy controls (HCs) were pre-incubated in vitro in the presence or absence of ShK-186, followed by stimulation with phorbol myristate acetate, calcium ionophore and brefeldin-A. The effect of ShK-186 on the cytokine production (IFNγ, TNFα, IL-4, IL-17, IL-21) within total and subsets of CD4+ T helper (CD4+TH) cells were assessed using flow cytometry. Results ShK-186 reduced the expression level of IFNγ, TNFα, IL-4, IL-17 and IL-21 in CD4+TH cells from patients with GPA in vitro. Further analysis performed on sorted CD4+T cell subsets, revealed that ShK-186 predominantly inhibited the cytokine production of CD4+TEM cells. ShK-186 treatment reduced the production of the pro-inflammatory cytokines to the level seen in CD4+ TH cells from HCs. Conclusions Modulation of cellular effector function by ShK-186 may constitute a novel treatment strategy for GPA with high specificity and less harmful side effects.
other
2025-10-24 | Granulomatous Reactions Following the Injection of Multiple Aesthetic Microimplants: A Complication Associated with Excessive Filler Exposure in a Predisposed Patient.
Background and Clinical Significance: Granulomatous reactions are rare but clinically significant complications of aesthetic procedures involving dermal fillers, particularly in individuals with underlying immune dysregulation. These reactions present diagnostic and therapeutic challenges, especially when associated with undiagnosed or latent autoimmune diseases. This case illustrates the interaction between filler composition, immune status, and the risk of delayed inflammatory responses, underscoring the need for thorough patient evaluation and individualized management strategies. Case Presentation: A 49-year-old woman developed delayed-onset subcutaneous nodules following midface augmentation with two filler types: a monophasic, cross-linked hyaluronic acid gel (concentration 20 mg/mL, 1.0 mL per side) injected into the deep malar fat pads, and a calcium hydroxyapatite suspension (30% CaHA microspheres in a carboxymethylcellulose carrier, 0.5 mL per side) placed in the subdermal plane along the zygomatic arch. The procedure was performed in a single session using a 22 G blunt cannula, with no immediate adverse events. High-resolution ultrasound demonstrated hypoechoic inflammatory nodules without systemic symptoms. A retrospective review of her medical history revealed a latent, previously undisclosed diagnosis of granulomatosis with polyangiitis (GPA). The immune-adjuvant properties of calcium hydroxyapatite likely triggered a localized pro-inflammatory response in this predisposed patient. A conservative, staged, non-invasive therapeutic protocol-saline infiltration, intradermal polynucleotide injections, and manual lymphatic drainage-achieved complete clinical and radiological resolution without systemic immunosuppression or surgical intervention. Conclusions: This case highlights the critical importance of pre-procedural immunological assessment in aesthetic medicine. Subclinical autoimmune conditions may predispose patients to delayed granulomatous reactions after filler injections. An individualized, conservative management strategy can effectively resolve such complications while minimizing the risks associated with aggressive treatment. Greater awareness of immune-mediated responses to dermal fillers is essential to ensure patient safety and optimize clinical outcomes.
2023-08-21 | BA.1/BA.5 Immunogenicity, Reactogenicity, and Disease Activity after COVID-19 Vaccination in Patients with ANCA-Associated Vasculitis: A Prospective Observational Cohort Study
Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited data on SARS-CoV-2 vaccination and prospective studies that have focused exclusively on AAV patients are lacking. In addition, there are safety concerns regarding the use of highly immunogenic mRNA vaccines in autoimmune diseases, and further studies investigating reactogenicity are urgently needed. In this prospective observational cohort study, we performed a detailed characterization of neutralizing antibody responses against omicron subtypes and provided a longitudinal assessment of vaccine reactogenicity and AAV disease activity. Different vaccine doses were generally well tolerated and no AAV relapses occurred during follow-up. AAV patients had significantly lower anti-S1 IgG and surrogate-neutralizing antibodies after first, second, and third vaccine doses as compared to healthy controls, respectively. Live-virus neutralization assays against omicron subtypes BA.1 and BA.5 revealed that previous SARS-CoV-2 vaccines result in an inadequate neutralizing immune response in immunocompromised AAV patients. These data demonstrate that new vaccination strategies including adapted mRNA vaccines against epitopes of emerging variants are needed to help protect highly vulnerable individuals such as AAV patients.
2022-12-01 | Herpes zoster infection after rituximab induction therapy in patient with myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis: a case report
Induction treatment with rituximab-an anti-CD20 monoclonal antibody-may increase the risk of varicella-zoster virus (VZV) reactivation in patients with antineutrophil-cytoplasmic-antibody-associated vasculitis (AAV). Our case report shows VZV reactivation following rituximab treatment in AAV patients. The recombinant zoster vaccine should be recommended before the start of induction treatment with rituximab.
2020-02-22 | Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients
Abstract Objective To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls. Methods Patients receiving rituximab ( n = 30), abatacept ( n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls ( n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 μg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F. Results Compared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls ( p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group ( p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs ( p = 0.03) and controls ( p = 0.001). Rituximab treatment was associated with large reduction (coefficient − 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients − 1.9 and − 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls. Conclusions Prime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab. Trial registration ClinicalTrials.gov , NCT03762824 . Registered on 4 December 2018, retrospectively registered
2013-06-01 | THU0306 Cellular and Humoral Responses to Varicella-Zoster Virus in Patients with Autoimmune Diseases
Herpes zoster (HZ) results from reactivation of varicella-zoster virus (VZV). Besides the symptoms of HZ, 8-27% of patients with herpes zoster develop postherpetic neuralgia (PHN), leading to debilitating pains. In particular elderly, HIV-patients and patients using immunosuppressive drugs are at increased risk for developing HZ and PHN. Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA) have a 5 to 16-fold increased risk compared to the general population. Use of immunosuppressive drugs is associated with the development of HZ in these patients. Aim of the study was to evaluate if the susceptibility of patients with autoimmune disease is due to decreased levels of cellular and/or humoral responses to VZV in these patients. A cross-sectional study on VZV-specific immunity was performed in 78 patients with SLE, 71 patients with GPA and 65 age- and sex-matched healthy controls (HC). In all individuals, serum antibody levels to VZV-glycoprotein (Gp) was measured by an in-house ELISA and, in a large proportion of tested individuals, compared to responses measured by VIDAS and Serion VZV-Gp ELISA. As control antibodies to Diphtheria (IBL-International) were measured in all participants. Cellular responses to VZV were measured in a large proportion of patients and controls by IFN-γ ELIspot assay and CFSE-dye dilution proliferation assay using cryopreserved PBMCs and UV-inactivated VZV as antigen. There was a strong correlation between the values measured with the in-house anti-Gp-VZV ELISA and VIDAS, and Serion anti-Gp-VZV ELISA (all p<0.0001). Antibodies to VZV were significantly (P=0.0005) increased in SLE patients (median 2019 mIU/ml, range 210 - ≥10000) compared to HC (median 1110 mIU/ml, range 110 - 8224). Values in GPA patients (median 1495 mIU/ml, range 20 - ≥10000) were not statistically different from values in HC. In contrast, antibodies against Diphtheria in both SLE and GPA patients were significantly (P<0.001) decreased compared to HC. Moreover, SLE and GPA patients had a significantly lower number of IFN-γ spot forming cells against VZV (P<0.05). Furthermore, the proliferation index (PI) of CD4+ T-lymphocytes was significantly (P<0,05) decreased in SLE patients compared to HC, but not in GPA patients. Patients with SLE have increased antibody levels against VZV compared to levels detected in HC, which cannot be explained by polyclonal hypergammaglobulinaemia as antibodies to Diphtheria were decreased in comparison to HC. Cellular immunity however, was decreased in these patients as well as in GPA patients. Our results suggest that increased prevalence of VZV in SLE and GPA patients is due to a poor cellular response to VZV. Vaccination strategies should not be based upon humoral immunity and should aim to boost cellular immunity against VZV. None Declared
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Drug Discovery Landscape
4 orphan drug designations for Granulomatosis with polyangiitis, including 1 approved therapy.
4 orphan drug designations for Granulomatosis with polyangiitis, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
(2R,3S)-2-(4-cyclopentylaminophenyl)-1-(2-fluoro-6-methylbenzoyl)piperidine-3-carboxylic acid(4-methyl-3-trifluoromethylphenyl)amide | small molecules | EMA | 2014-11-19 | 2022-01-19 | Vifor Fresenius Medical Care Renal Pharma France |
gusperimus trihydrochloride | small molecules | FDA | 2011-06-29 | — | Nordic Group B.V. |
Gusperimus trihydrochloride | small molecules | EMA | 2001-03-29 | — | Nordic Group B.V. |
Etanercept | proteins | FDA | 1999-04-06 | — | Immunex Corporation |
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