antibodies

2026-08-14 | Interferon-targeted therapy with anifrolumab in monogenic pediatric systemic lupus erythematosus due to C1q deficiency: a case report.

Monogenic Pediatric systemic lupus erythematosus (SLE) secondary to complement deficiencies, including C1Q deficiency caused by C1QA mutations, is a rare and severe type of SLE that can be characterized by early onset and refractory disease. Inhibiting the interferon pathway has proved to be an effective treatment option, although there is little evidence in monogenic pediatric SLE. We describe a 10-year-old female with genetically-verified C1Q deficiency who had persistent and severe mucocutaneous disease, with recurrent skin rash, ulcerations, and oral sores, despite long-term immunosuppressive and biologic treatment. After a disease flare, the patient was started on anifrolumab, a monoclonal antibody against type I interferon receptor. She showed significant clinical improvement and full recovery of mucocutaneous lesions, restoration of laboratory parameters and successful discontinuation of corticosteroids after the seventh monthly infusion. It was well tolerated with no serious side effects. The case demonstrates the possible effectiveness and safety of anifrolumab in the treatment of refractory cutaneous manifestations in children with monogenic pediatric SLE, which is linked to interferon pathway dysregulation. Further studies are needed to establish its role in this population.

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2026-08-12 | Achievement of real-world adapted DORIS remission targets among patients with systemic lupus erythematosus initiating belimumab in the USA: A retrospective, observational, cohort study.

IntroductionRemission is a key treatment goal associated with improved patient outcomes in systemic lupus erythematosus (SLE), often measured by Definition of Remission In SLE (DORIS) criteria. In a post hoc analysis of clinical trial data, belimumab, a B-cell modulator targeting the central immunopathogenic pathway in SLE, plus standard therapy, improved DORIS remission rates versus placebo plus standard therapy; however, US real-world remission rates remain limited. Measuring DORIS criteria in real-world clinical practice is challenging because required variables, particularly the SLE Disease Activity Index (SLEDAI) component, are often unavailable or incompletely recorded. Therefore, we evaluated an adapted DORIS definition for real-world datasets and examined predictors of remission among US patients initiating belimumab.MethodsThis retrospective observational cohort study analysed data for patients with SLE initiating belimumab from the OM1 PremiOM™ SLE dataset, comprising electronic health records/healthcare claims data (2013-2024) for patients with SLE. The primary outcome was probability of achieving adapted DORIS remission at 28, 48, and 52 weeks post-treatment initiation, defined as clinician-recorded SLEDAI (crSLEDAI) or estimated SLEDAI (eSLEDAI) = 0, Physician Global Assessment (PGA) <2 on a 0-10 numerical rating scale, and prednisone-equivalent dose ≤5 mg/day. Kaplan-Meier estimates provided remission probabilities and logistic regression identified predictors of remission.ResultsMost patients (N = 398) were White, female, from the Southern region of the USA, and had commercial insurance. The probability of achieving adapted DORIS remission reached 28.3% (95% confidence interval: 19.8-35.9) by 52 weeks post-belimumab initiation. Older patients (≥50 years), non-White individuals, and patients with cr/eSLEDAI ≤5 demonstrated slightly higher remission probabilities than their counterparts; however, estimates differed by censoring approach, and confidence bounds overlapped. Adjusted multivariable analysis confirmed increasing age, non-White race, and cr/eSLEDAI ≤5 as significant predictors of remission.ConclusionThis study demonstrates the application of an adapted DORIS definition to large real-world observational datasets. The probability of adapted DORIS remission in US patients initiating belimumab was similar to rates reported in observational studies outside the USA, supporting the real-world effectiveness of belimumab. The increased likelihood of remission in patients with cr/eSLEDAI ≤5 supports the benefits of initiating belimumab treatment early in the disease course.

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2026-08-08 | Subcutaneous Belimumab Demonstrates Consistent Steady-State Pharmacokinetics and is Well Tolerated in Paediatric Patients with SLE in China: An Open-Label Study.

This study assessed pharmacokinetics and safety of subcutaneous (SC) belimumab in Chinese paediatric patients with systemic lupus erythematosus (cSLE) who previously received intravenous (IV) belimumab; only the IV form is approved for cSLE in China. This single-arm, open-label, 12-week bridging study (GSK Study 217091) characterised belimumab 200 mg SC exposure in Chinese paediatric patients (5-17 years) with cSLE who completed the 48-week IV belimumab Phase 4 trial (GSK Study 213560). Safety and tolerability of SC belimumab on-treatment and in a 16-week follow-up period were also assessed. Patients were categorised based on weight; data were summarised using descriptive statistics. Overall, 16 patients were enrolled (≥ 15- < 30 kg, n = 1; ≥ 30- < 50 kg, n = 5; ≥ 50 kg, n = 10) with a mean age of 12.9 years. The geometric mean approximate Cmax (3 days post-administration) after the first and last dose were 92.44, 63.41 and 68.87 μg/mL, and 28.01, 85.11 and 88.61 μg/mL for the three weight groups, respectively. The geometric mean Ctrough at steady state were, 20.44, 71.57 and 85.55 μg/mL for the ≥ 15- < 30 kg, ≥ 30- < 50 kg and ≥ 50 kg weight groups, respectively. Thirteen patients (81%) reported ≥ 1 AE. No SAEs, severe AEs, AESIs, AEs resulting in belimumab discontinuation, deaths, or local injection site reactions were reported. SC belimumab demonstrated expected steady-state exposure and tolerability in Chinese paediatric patients with SLE, supporting its use in this patient population. GSK Study 217091; NCT05917288.

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2026-08-07 | First experience with obinutuzumab in a juvenile-onset systemic lupus erythematosus patient with rituximab-associated posterior reversible encephalopathy syndrome

Juvenile-onset systemic lupus erythematosus (JSLE) is characterized by higher disease activity and greater treatment burden than adult-onset disease, often requiring intensive immunosuppression. Rituximab is used in refractory cases, but re-exposure may not be possible when adverse events such as posterior reversible encephalopathy syndrome (PRES) occur. Obinutuzumab, a type II anti-CD20 monoclonal antibody, has shown efficacy in adult patients with lupus nephritis and in those with active SLE, yet pediatric experience is limited. We report an 11-year-old boy with JSLE and lupus nephritis who developed lupus pneumonitis and increased renal activity while receiving conventional therapy. Rituximab was initiated but complicated by PRES six hours after the first infusion, leading to discontinuation. Despite cyclophosphamide induction and mycophenolate mofetil plus cyclosporine maintenance, he later experienced a disease flare with malar rash, low complement levels, and rising anti-dsDNA titres. Because rituximab re-use was avoided, obinutuzumab was selected as an alternative anti-CD20 agent in the setting of a disease flare. A body-surface-area-adjusted regimen derived from the adult protocol was administered in two infusions under close monitoring. Following obinutuzumab, complement levels normalized, anti-dsDNA declined, and SLEDAI-2K decreased from 6 to 2, and peripheral B-cell depletion was confirmed at eight weeks and maintained at six months, without neurological or infectious complications over six months of follow-up. This case suggests that obinutuzumab may be a feasible alternative anti-CD20 option in rituximab-intolerant JSLE, pending results from ongoing pediatric clinical trials.

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2026-07-28 | Characteristics and outcomes of anti-Ku antibody-associated interstitial lung disease: a retrospective study of 60 patients.

Anti-Ku antibodies (Abs) are rare and detected in various autoimmune diseases (AIDs), presenting in various phenotypes, potentially affecting different organs including the lungs. This study aimed to describe the characteristics and evolution of interstitial lung disease (ILD) in anti-Ku-positive patients. An observational, multicentre, retrospective study was conducted across 10 French University Hospitals between January 2010 and June 2025, including patients with anti-Ku Abs with ILD. Clinical data and all pulmonary function tests and chest CT scans available were reviewed for this study. ILD progression was defined using criteria inspired by the American Thoracic Society/European Respiratory Society/Japenese Respiratory Society/Asociación Latinoamericana de Tórax Clinical Practice Guidelines, applied across the entire follow-up period rather than within the 12-month timeframe, to capture all clinically meaningful progression events. To account for event timing, time to ILD progression was analysed as a time-to-event outcome using Cox proportional hazards models. Among 154 anti-Ku-positive patients (51 with idiopathic inflammatory myopathy, 46 with systemic lupus erythematosus, 30 with Sjögren's disease, 27 with systemic sclerosis), 60 (39%) had ILD (68% women, median age 56 years). The predominant ILD pattern was fibrotic non-specific interstitial pneumonia (27%, n=16). ILD was already present at AID diagnosis in 48 patients (80%). Forty-five (75%) patients progressed after a median time of 4 (2-11) years. Male sex (adjusted HR (aHR) 2.7; 95% CI 1.4 to 5.2) was associated with ILD progression. When the 12-month cut-off was strictly applied, only six patients fulfilled the progressive fibrosing ILD definition. Baseline pulmonary fibrosis was present in 34 (57%) patients and was associated with a reduced survival when adjusting for age at ILD diagnosis and cardiac involvement (aHR 6.5, 95% CI 1.5 to 28.2). ILD occurred in 39% of anti-Ku-positive patients and progressed in 75% of them, underscoring the importance of systematic ILD screening and monitoring in these patients.

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small molecules

2026-08-15 | Expanding the clinical spectrum of DNASE1L3-associated monogenic lupus: A case series of 4 syrian pediatric cases.

DNASE1L3 deficiency is a rare autosomal-recessive monogenic form of systemic lupus erythematosus, characterized by defective clearance of extracellular DNA, leading to immune-complex formation, autoantibody production, and systemic inflammation. While early-onset lupus nephritis and hypocomplementemic urticarial vasculitis are hallmark features, the full clinical spectrum remains incompletely understood, particularly in pediatric populations. We report 4 cases from 2 unrelated consanguineous Syrian families, including 1 genetically confirmed case with a pathogenic DNASEI L3 variant, 1 case harboring a homozygous DNASEI L3 variant of uncertain significance, and 2 phenotypically concordant siblings without genetic testing. Clinical, laboratory, and histopathologic data were reviewed to characterize disease manifestations, organ involvement, serologic profiles, and therapeutic outcomes. All patients presented with recurrent fever, cutaneous rash, and musculoskeletal involvement, with notable variability in autoantibody profiles, renal pathology, and disease severity. Genetic analysis identified a homozygous pathogenic DNASEI L3 variant in case 3 and a homozygous DNASEI L3 variant of uncertain significance in case 1, supporting a clinically suspected DNASEI L3-associated monogenic lupus-spectrum disease. Renal involvement ranged from IgA glomerulonephritis to class IV lupus nephritis. Ocular manifestations, including conjunctival congestion and papilledema, were observed in 3 patients, highlighting an underrecognized feature. Therapeutic responses varied: 1 patient remained stable on baricitinib, while 2 patients succumbed to severe neurologic or renal complications. This series underscores the heterogeneous phenotypic spectrum of DNASEI L3-associated disease, including atypical seronegative presentations and diverse renal pathology. DNASEI L3-associated disease should be considered in children with early-onset vasculitic rash, hypocomplementemia, and nephritis, regardless of classical autoantibody status. Our cases expand the known clinical spectrum, emphasize the potential for ocular involvement, and suggest a role for targeted therapies such as JAK inhibitors in interferon-driven disease. Early genetic testing is essential for timely diagnosis and management of this potentially life-threatening condition.

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2026-08-11 | Free mycophenolic acid exposure for therapeutic drug monitoring in paediatric lupus nephritis: associations with treatment response and haematologic toxicity.

This study aimed to evaluate the associations of free mycophenolic acid (f-MPA) concentration and total MPA (t-MPA) concentration with treatment response and haematologic toxicity and to determine whether f-MPA provides additional safety-related value for therapeutic drug monitoring (TDM) in patients with paediatric lupus nephritis (LN) treated with mycophenolate mofetil (MMF). Sixty-five patients with paediatric LN receiving MMF were prospectively enrolled. The t-MPA and f-MPA were measured simultaneously using validated ultrafiltration and LC-MS/MS. Full pharmacokinetic profiles were obtained over 12 hours, and area under the concentration-time curve (AUC) was calculated for t-MPA (t-MPA-AUC) and f-MPA (f-MPA-AUC). Univariate analysis identified factors influencing efficacy (relapse-free survival) and adverse drug reaction (ADR) over 12 months. Receiver operating characteristic (ROC) curves established predictive thresholds and Kaplan-Meier methods analysed time-to-event. The 12-month relapse-free rate was 78.7% (95% CI 66.6% to 90.9%). Both t-MPA-AUC and f-MPA-AUC significantly correlated with relapse-free survival (ROC AUC 0.70 each; optimal thresholds: t-MPA-AUC=31.63 µg·h/mL, f-MPA-AUC=354.45 ng·h/mL). The average remission duration above these thresholds was 10.88 and 11.00 months. The overall MMF-related ADR incidence was 25.2%, including 17 haematological events (26.2%). The t-MPA-AUC, f-MPA-AUC, glucose, β2-microglobulin and C3 were haematological ADR risk factors. The f-MPA-AUC independently predicted haematological ADRs (optimal threshold: 492.96 ng·h/mL; specificity 86.2%). Both t-MPA-AUC and f-MPA-AUC effectively predict MMF efficacy in paediatric LN. However, f-MPA-AUC demonstrates superior predictive value for safety outcomes, specifically haematological ADRs. This supports f-MPA as a potentially better TDM metric for optimising MMF therapy safety in this population.

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2026-07-30 | Comparative Efficacy and Safety of Mycophenolate Mofetil Versus Cyclophosphamide As Induction Therapy for Lupus Nephritis: A Systematic Review and Meta-Analysis.

Lupus nephritis (LN) is a serious and potentially fatal systemic lupus erythematosus complication that causes substantial morbidity and may progress to end-stage kidney disease. Traditionally, cyclophosphamide (CYC) has been prescribed as induction therapy for LN. However, there has been a trend toward using mycophenolate mofetil (MMF) as an alternative treatment due to concerns of toxicity. This systematic review and meta-analysis evaluated the comparative safety and efficacy of MMF to CYC as induction therapy in LN. PubMed, Embase, Scopus, and Cochrane CENTRAL databases were searched comprehensively from their inception through January 2026. Randomized controlled trials and observational studies comparing MMF and CYC in adult or pediatric patients with LN were included. Complete renal remission, partial renal remission, overall renal response, mortality, infections, GI adverse events, leukopenia, menstrual disorders, and alopecia were evaluated as outcomes. Overall, 12 studies involving 1,502 patients were analyzed. MMF was significantly associated with a higher rate of complete renal remission than CYC (risk ratio (RR) = 1.11, 95% confidence interval (CI): 1.01-1.22). No significant difference between the two therapies in partial renal remission, total renal response, mortality, infection, GI adverse events, or leukopenia. However, MMF was associated with significantly lower risks of menstrual disorders (RR = 0.47, 95% CI: 0.27-0.82) and alopecia (RR = 0.32, 95% CI: 0.15-0.70). Overall, MMF appears to be as effective as CYC for the induction treatment of LN, while exhibiting a more favorable safety profile regarding reproductive and cosmetic adverse events. The results indicate that MMF is an effective and safer induction agent for patients with LN.

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2026-07-28 | Childhood-Onset Lupus Nephritis in the Era of Triple Therapy and Steroid Minimization.

Childhood-onset lupus nephritis (cLN) should no longer be framed as a smaller version of adult lupus nephritis. It is a high-stakes pediatric kidney disease in which immune injury, treatment toxicity, growth, puberty, fertility, adherence, and transition to adult care intersect over decades. Approximately 10-20% of systemic lupus erythematosus begins in childhood, and 40-60% of affected children develop lupus nephritis. Regional cohorts report even higher renal involvement in some populations, including 65-73% among Saudi children with SLE. Contemporary guidance has moved from prolonged high-dose glucocorticoids and cyclophosphamide-dominant treatment toward biopsy-driven, treat-to-target care built around mycophenolic acid analogues, hydroxychloroquine, nephroprotection, rapid steroid tapering, and selected belimumab- or calcineurin-inhibitor-based triple therapy. This Viewpoint argues that the central question in cLN is no longer simply how to induce remission, but how to produce a durable kidney response early enough, with sufficiently low cumulative toxicity, to preserve kidney function and childhood development. Pediatric practice must therefore combine adult trial evidence with child-specific caution, explicit adherence strategies, fertility and growth protection, and structured transition planning. The aim should be efficacy without toxicity: not undertreatment, but intelligent, sustainable, developmentally informed treatment.

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2026-07-25 | T cell exhaustion: a two-sided blade in systemic lupus erythematosus, from molecular mechanisms to clinical translation.

Dysregulated immune responses and extensive inflammatory damage to several organs are hallmarks of systemic lupus erythematosus (SLE), a highly heterogeneous systemic autoimmune disease that significantly impairs patients' quality of life and prognosis. Persistent antigenic stimulation causes T cell exhaustion (Tex), a unique functional state that is carefully controlled by exogenous, temporal, and spatial factors. Tex plays a special bidirectional regulatory role in SLE: on the one hand, it exerts a protective effect by suppressing the excessive activation of autoreactive T cells, thereby mitigating immune-mediated damage to target organs; on the other hand, abnormal exhaustion of specific T cell subsets leads to a loss of immunoregulatory function and may even promote the secretion of pro-inflammatory cytokines, thereby exacerbating pathological damage. Therapeutic strategies based on this dual mechanism focus on restoring immune homeostasis by enhancing protective exhaustion and inhibiting pathogenic exhaustion processes; this can be achieved through precise regulation of exhausted T cell subsets, improvement of the immune microenvironment, and interventions targeting key signalling pathways. This article provides a systematic review of the core molecular mechanisms and phenotypic characteristics of Tex, highlighting the latest research advances regarding its bidirectional regulatory role in SLE, and discusses in detail relevant diagnostic biomarkers and potential targeted therapeutic strategies. It aims to provide new insights and a theoretical basis for the clinical assessment, personalised treatment, and targeted drug development of SLE.

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proteins

2026-02-23 | Case Report: Telitacicept in the treatment of cSLE-APS: novel therapeutic perspectives on autoimmune thrombotic diseases in children.

Thrombotic antiphospholipid syndrome (APS) in Childhood-onset systemic lupus erythematosus (cSLE) remains a therapeutic frontier. Here, we report the first case of telitacicept (a TACI-Fc fusion protein)- induced remission in cSLE related antiphospholipid syndrome (cSLE-APS), where targeted dual BAFF(B cell-activating factor)/APRIL(a proliferation-inducing ligand) inhibition resolved life-threatening infarctions and achieved sustained disease control. During treatment, corticosteroids were successfully discontinued within six months, and a lupus low disease activity state (LLDAS) was maintained. Our findings indicate that telitacicept's unique ability to regulate B-cell activity could target the dual pathology of cSLE-APS, offering a new therapeutic approach for this serious condition.

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2025-11-08 | Juvenile systemic lupus erythematosus complicated with posterior reversible encephalopathy syndrome: a case report and literature review.

Posterior reversible encephalopathy syndrome (PRES) is an acute or subacute neurological syndrome with clinical manifestations including headache, vision loss, altered mental status, and seizures. Magnetic resonance imaging(MRI) can assist in clarifying the diagnosis. Systemic lupus erythematosus (SLE) is an autoimmune disease, and the occurrence of PRES is infrequent, especially in children with SLE. Our patient was initially diagnosed with juvenile systemic lupus erythematosus involving the skin, joints, and kidneys. The patient was treated with glucocorticoids and cyclophosphamide, which led to a partial improvement in symptoms. However, the patient experienced neurological symptoms and elevated blood pressure, and head MRI revealed swelling and diffuse damage to the bilateral occipital parietal gyrus. The patient was diagnosed with PRES. The symptoms were relieved after actively lowering blood pressure, dehydrating with mannitol, and treating with glucocorticoids, cyclophosphamide, and telitacicept. Six months later, no abnormalities were observed in the follow-up head MR image. We searched PubMed to review the characteristics of 15 children with SLE who developed PRES, and most of them recovered after active treatment. Various factors can lead to complications of PRES in paediatric patients with systemic lupus erythematosus. In our patient, the likely cause was the high disease activity of SLE. This review revealed that juvenile SLE cases accompanied by PRES are often associated with lupus nephritis, hypertension, and high disease activity. Most patients recover with timely and active treatment, with only a few experiencing recurrence.

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2025-11-01 | Neutrophil Extracellular Traps and DNASE balance in pre and post-treatment pediatric SLE patients 4076

Abstract Description Pediatric systemic lupus erythematosus (pSLE) is a multisystemic chronic autoimmune disease with high renal involvement. Neutrophil extracellular traps (NETs) are considered a potential source of self-antigen, leading to autoantibody production. NETs have also been shown to play a role in kidney pathology leading to lupus nephritis (LN). Low DNASE activity and mutations have been associated with lupus. Plasma was obtained from 18 pSLE treatment-naïve patients (before induction), 10 post-treatment patients and 12 age- and sex-matched healthy children. 67% of treatment naïve patients were diagnosed with biopsy proven LN. Induction was started at diagnosis with corticosteroids, primarily with mycophenolate, cyclophosphamide, or rituximab, depending on disease severity. Treatment response was measured by SELENA-SLEDAI score, dsDNA antibody levels, and urine protein/creatine ratios; all of which decreased post-treatment. Accumulation of NETs in circulation was observed pre-treatment with significant reductions post-treatment. Plasma from pre-treatment pSLE patients failed to degrade NETs efficiently which was restored after treatment. There was a defect in DNASE1 and DNASE1L3 activity pre-treatment. We observed an increase in anti-DNASE1L3 antibodies pretreatment which were significantly reduced post-treatment. Purified IgG from pre-treatment patients was able to inhibit DNASE1L3 activity whereas post-treatment IgG failed to do that. No DNASE1L3 RC206 mutation was detected Topic Categories Therapeutic Approaches to Autoimmunity (THER)

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2025-10-15 | Cytokine-induced memory-like natural killer cells in systemic lupus erythematosus patients.

BACKGROUND: Natural killer (NK) cell abnormalities may contribute to the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-15, an immunoregulatory cytokine crucial for NK survival, is overexpressed in SLE patients. Cytokine-induced memory-like (CIML) NK cells, which are NK cells pre-activated with short-term IL-12+IL-15+IL-18 followed by incubation with low-dose IL-15 for 1-2 weeks, exhibit enhanced NK effector function upon re-stimulation. METHODS: We collected blood samples from 54 patients with SLE and 38 healthy volunteers. Extended IL-15 stimulation of peripheral blood mononuclear cells (PBMCs) was performed. Surface marker analysis, IFN-γ, TNF-α production, and cytotoxicity evaluation were conducted. Next, we generated CIML NK cells by culturing PBMCs with IL-12+IL-15+IL-18. The influence of short-term and long-term IL-15 treatment on CIML NK cells was assessed. Finally, we examined the effect of re-stimulation with IL-12+IL-15+IL-18 on CIML NK cells from SLE patients and healthy controls. Cytotoxicity, CD107a degranulation, and surface marker expression were analyzed. RESULTS: We found that 1. The percentage of CD3-CD56+ NK cells was initially decreased in SLE patients compared with controls, but was enhanced after long-term IL-15 incubation; 2. Long-term IL-15 stimulation facilitated the conversion from CD3-CD56dim to CD3-CD56bright NK cells; 3. CIML NK cells were successfully generated in SLE patients, showing increased percentages of CD3-CD56+ and CD3- CD56bright NK cells and a concomitant decrease in CD3-CD56dim NK cells; 4. SLE CIML NK cells showed decreased IFN-γ, CD69, CD94, NKG2A, NKG2C, NKP30, NKP44, NKP46, and granzyme B expression compared with healthy controls; 5. On day 8, re-stimulation with IL-12+IL-15+IL-18 further enhanced the expression of IFN-γ, CD69, CD94, NKG2A, perforin, and granzyme B expression on SLE CIML NK cells; 6. Granzyme B expression in SLE CIML NK cells was higher on day 8 than on day 15. CONCLUSION: Our findings revealed phenotypic differences and functional deficiencies in SLE CIML NK cells. Further investigation into the role of SLE CIML NK cells in providing antiviral and anti-tumor responses is warranted. CLINICAL TRIAL NUMBER: Not applicable.

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2025-07-17 | Telitacicept for systemic lupus erythematosus: protocol of a systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a chronic and complex multisystem autoimmune disease with high mortality. Telitacicept is a new strategy for the treatment of SLE, inhibiting the maturity, proliferation and differentiation of B cells, and thus, reduces disease activity. However, the effectiveness and safety of telitacicept in patients with SLE are not yet established. Five English databases (Pubmed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature) and four Chinese databases (China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database and Sinomed) will be searched from database inception to 1 June 2025. Two investigators will independently conduct study selection, data extraction and quality assessment. Outcomes include disease activity, incidence of flares, organ damage, several immune-related laboratory parameters and adverse events. Risk ratio with 95% CI and mean difference or standardised mean difference will be used as measures of effect sizes, in order to pool the data using either a random-effect model or fixed-effect model according to the heterogeneity of studies. Subgroup analysis and sensitivity analysis will be performed to explore the source of heterogeneity and evaluate the robustness of the results. We will use the Risk of Bias 2 tool and Risk of Bias In Non-Randomized Studies of Interventions tools to assess the quality of the included studies, and use the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system to assess the certainty of evidence. No ethical approval is required since this review is based on previously published studies. The findings of this study will be presented at international conferences or published in a peer-reviewed journal. CRD42024558180.

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cell therapies

2026-07-16 | CAR-based cellular therapy for refractory systemic lupus erythematosus: an overlap-controlled systematic review.

To define the current evidence for CAR-based cellular therapy in relapsed or refractory systemic lupus erythematosus (SLE) by resolving overlapping reports and synthesising patient-level phenotype, safety and efficacy data. The primary purpose was evidence mapping with duplicate-count control; mechanistic immune-reset interpretation and platform differences were treated as secondary, hypothesis-generating questions rather than formal comparative-effectiveness analyses. PubMed, Embase and Web of Science were searched for reports published from January 2020 to March 2026. Eligible records described CAR-based cellular therapy in relapsed, refractory or organ-threatening SLE. Overlapping publication streams were collapsed into independent study units, and a deduplicated patient-level master dataset was constructed. Outcomes were summarised descriptively using conservative exact patient-level attribution, with endpoint evaluability reported separately from observed outcome proportions. Twenty-one independent study units comprising 114 counted patients were included. The cohort was predominantly female (100/114, 87.7%), young (median age 32.0 years) and heavily pretreated, with renal involvement in 89 patients (78.1%). Autologous CD19 CAR-T and BCMA-containing platforms accounted for most treated patients, with additional allogeneic CAR-T and CAR-NK experience. Among exactly evaluable rows, clinical response was documented in 45 of 45 patients, DORIS remission in 13 of 15, SLE Responder Index-4 response in 20 of 20, renal improvement in five of five and drug-free remission in 28 of 58. These proportions should not be read as pooled response rates because exact endpoint denominators were small or incomplete for several outcomes. Cytokine release syndrome was usually low grade, and immune effector cell-associated neurotoxicity syndrome was uncommon. Severe inflammatory toxicities occurred in selected paediatric or highly inflammatory settings. Endpoint evaluability varied substantially across studies. CAR-based cellular therapy shows substantial promise as an immune-reset strategy for refractory SLE, particularly in renal-dominant disease. However, current evidence remains early, uncontrolled and incompletely reported. Sparse exactly evaluable denominators, publication bias, selective outcome reporting and short follow-up preclude definitive platform comparisons, supporting standardised prospective studies with harmonised efficacy, immune-reconstitution and toxicity endpoints. https://www.crd.york.ac.uk/prospero/, identifier CRD420261330006.

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2026-06-15 | A symposium update on the key perspectives in systemic sclerosis and systemic lupus erythematosus.

The fourth LBMR-Tim (Toulouse Referral Medical Laboratory of Immunology) symposium was convened on December 15th, 2025, in Toulouse, France, to discuss recent advances in the understanding and management of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Pathophysiological mechanisms underlying SSc and SLE were discussed from a genetic perspective, with particular emphasis on the X-chromosomal TLR7/TLR8 locus and the interferon signaling pathway. Cellular aspects were explored, highlighting the critical roles of regulatory T cells (Tregs), exhausted T cells, macrophage polarization, and endothelial cells. At the translational research frontier, significant initiatives are underway within the framework of the European Autoimmunity Standardization Initiative (EASI) aimed at enhancing routine biomarker application for diagnosis, disease monitoring, and prognostic considerations. Emerging biomarker candidates promise potential for improving prognostic assessment and follow-up in lupus nephritis (e.g., urinary sCD163/creatinine ratio), cardiovascular complications and vasculopathy associated with SSc (e.g., dephosphorylated-uncarboxylated matrix Gla protein [dp-ucMGP] and endothelial progenitor cells), as well as therapeutic response evaluation (e.g., IGRA-PHA assays and proteomic methodologies). Therapeutically, a paradigm shift is underway with the development of efficacious mono- and multi-targeted antibody treatments alongside cellular therapies designed to eliminate B cells through chimeric antigen receptor (CAR) T cells or to re-establish immune regulation through Treg restoration. The integration of these therapeutic modalities necessitates further investigation to optimize individualized patient selection and management strategies. The multidisciplinary expert panel advocates for a comprehensive approach encompassing fundamental science, translational research, clinical expertise, and therapeutic innovation to advance in the management of these two complex syndromes.

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2026-05-27 | Beyond Hematology-Current Insights into Chimeric Antigen Receptor (CAR) T-Cell Therapy for Skin and Connective Tissue Disorders.

Chimeric antigen receptor (CAR) T-cell therapy represents a major advance in modern immunotherapy. This narrative review summarizes evidence from the past five years, including case reports, case series, and clinical trials, on its application beyond hematologic malignancies, focusing on autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), as well as solid tumors including melanoma and primary cutaneous lymphomas. CD19-directed CAR T-cells have demonstrated clinical benefits in SLE and SSc, with sustained immune reset, reduced autoreactive antibody levels, and clinical improvement. In melanoma, CAR T-cells targeting GD2, cMET, and CD20 have shown in vivo expansion and tumor infiltration; however, clinical efficacy remains limited, with transient stabilization or disease progression in most patients. In primary cutaneous lymphomas, early-phase studies with anti-CD70 and anti-CCR4.30 CAR T-cells indicate partial tumor regression and disease stabilization, often requiring additional therapy. Key challenges include limited durability of immune reset due to persistent plasma cells in autoimmune disorders, tumor heterogeneity, antigen loss or overlap, infiltration barriers, resistance mechanisms, and T-cell depletion in solid tumors, collectively reducing response durability and safety. The main toxicities include grade 1-2 cytokine release syndrome and rare hematologic complications, while immune effector cell-associated neurotoxicity syndrome is uncommon. Clinical translation remains limited and requires larger studies to improve efficacy and define safety profiles.

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2026-05-20 | Aortic Valve Neocuspidization in Libman-Sacks Endocarditis.

Libman-Sacks endocarditis (LSE) is a noninfective thrombotic endocarditis frequently associated with antiphospholipid syndrome (APS) and/or systemic lupus erythematosus. Valvular obstruction, if it occurs, may require urgent surgery. Two women with APS and systemic lupus erythematosus presented with severe aortic valve (AV) obstruction due to LSE. Both underwent AV neocuspidization (AVNeo) using the autologous pericardium "Ozaki technique." The procedures were successful, and the postoperative course was uneventful for each. At the 2- and 3-year follow-up, both patients were doing well with good AV function and maintained competence. Mechanical valves are traditionally preferred for APS patients because of the inherent need for lifelong anticoagulation. However, AVNeo may offer superior hemodynamics, avoidance of traditional lifelong warfarin therapy, and improved quality of life, particularly in younger patients desiring pregnancy. To our knowledge, these cases represent the first reported AVNeo cases for LSE. AVNeo represents a promising surgical alternative in APS-associated LSE, combining favorable outcomes and potential anticoagulation benefits.

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2026-05-18 | Homozygous C1qA Deficiency Presenting as Early-Onset Systemic Lupus Erythematosus: A Case Report With a Literature Review.

Childhood-onset systemic lupus erythematosus (cSLE) can be particularly severe when associated with inborn errors of immunity. Hereditary C1q deficiency is an exceptionally rare complement disorder that confers a very high risk of early, aggressive lupus. Reporting this case highlights the need to consider complement deficiencies in young children presenting with lupus-like features and recurrent infections and illustrates the diagnostic value of integrating immunologic and genetic testing. A 3-year-old girl presented with recurrent infections, a photosensitive rash, and persistent leukopenia, raising clinical suspicion for an underlying complement deficiency in the context of cSLE. Laboratory evaluation showed strongly positive antinuclear antibody (ANA) and anti-SSA antibodies, with normal C3 and C4 levels but markedly reduced CH50. Lymphocyte subset analysis by flow cytometry was unremarkable. Western blot analysis and whole-exome sequencing identified a homozygous nonsense variant in C1qA (c.622C > T; p.Gln208 ∗), confirming complete hereditary C1q deficiency. Despite treatment with corticosteroids and hydroxychloroquine, the patient's disease activity remained suboptimal, leading to consideration of hematopoietic stem cell transplantation as a definitive therapeutic option. This case emphasizes the importance of early recognition and systematic evaluation of complement deficiencies in pediatric patients with lupus manifestations and recurrent infections. Identifying hereditary C1q deficiency has crucial implications for diagnosis, prognosis, and timely selection of advanced therapies, including hematopoietic stem cell transplantation, in severe forms of cSLE.

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2026-07-13 | Autoimmune diseases in the era of COVID-19: emerging mechanisms, clinical implications, vaccine considerations, and future directions.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted a complex, bidirectional relationship between SARSCoV-2 infection and autoimmune diseases. This review examines how SARS-CoV-2 infection influences the incidence, progression, and outcomes of five major autoimmune conditions: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and Guillain-Barré syndrome. Patients with autoimmune diseases are at increased risk of severe COVID-19 due to intrinsic immune dysregulation and the use of immunosuppressive therapies, both of which impair antiviral host defenses. Conversely, COVID-19 has been implicated in the initiation and exacerbation of autoimmune responses through mechanisms such as molecular mimicry and bystander activation. Concerns have also arisen regarding the safety and efficacy of COVID-19 vaccines in immunocompromised populations. Although vaccines are generally tolerated in these individuals, certain immunosuppressive therapies may attenuate humoral and cellular immune responses. Strategies such as adjusting immunosuppressive regimens and optimizing the timing of vaccination have been proposed to improve vaccine efficacy. Disease-specific considerations are essential to balance infection risk with adequate control of autoimmune activity. Overall, this review underscores the importance of individualized treatment strategies, close clinical monitoring, and interdisciplinary care in managing patients with autoimmune diseases during the COVID-19 pandemic. A deeper understanding of these interactions will be critical for improving patient outcomes and preparing for future pandemics involving immune-mediated diseases.

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2026-03-27 | Knockdown of the long isoform of the prolactin receptor selectively targets pathogenic immune cells in systemic lupus erythematosus and averts glomerular pathology.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation in multiple organ systems. While a clinical association between elevated levels of the hormone/cytokine, prolactin (PRL), and exacerbation of SLE has been recognized for some time, little is known about the mechanisms through which PRL affects the course of this disease. Here, we show that immune cells in SLE have aberrant splicing of the prolactin receptor (PRLR) such that the ratio of the long to short splice variants is increased. To determine whether the change in PRLR isoform expression was causal in this disease, we used a splice-modulating oligomer (SMO) that knocked down expression of the long splice variant (LFPRLR). Using patient samples ex vivo, SLE-prone mice in vivo, high-dimensional flow cytometry and single-cell RNA-sequencing, we demonstrate that the aberrant PRLR isoform expression in SLE both directly and indirectly drives production of autoreactive immune cell phenotypes. Thus, LFPRLR knockdown decreased the expression of type I interferon signaling/response genes known to be biomarkers and hub genes for SLE, reduced immunoglobulins with signatures considered autoreactive, and averted glomerular kidney damage in SLE-prone mice. Importantly, LFPRLR knockdown reduced pathogenic B cells and other immune subsets that drive B-cell activation, without negative impact on healthy donor counterparts. Current treatments for SLE adversely affect healthy cells and do not concurrently eradicate multiple pathogenic immune subsets. Since LFPRLR SMO does not share these disadvantages, knockdown of the LFPRLR represents a potential treatment strategy for SLE that merits further investigation.

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2026-03-19 | Genetic and phenotypic landscape of monogenic lupus: insights from an international cohort.

To characterise the clinical, immunologic and molecular genetic features of monogenic lupus in a large, ethnically diverse paediatric cohort and to evaluate genotype-phenotype correlations. We conducted a retrospective multicentre study of 100 children with genetically confirmed monogenic lupus diagnosed before the age of 14 years. Patients were enrolled between 2000 and 2025 from centres in Saudi Arabia, Iran, Russia, Italy, Palestine and Oman. Demographic data, clinical manifestations, immunological findings, genetic results, treatments and outcomes were systematically analysed. Multivariable logistic regression was used to evaluate associations between specific genotypes and clinical phenotypes. The median age at onset was 24 months, with 69% of patients carrying homozygous pathogenic mutations. The most frequently implicated genes were C1Q (26%) and DNASE1L3 (25%), representing complement and type I interferon pathways, respectively. Mucocutaneous (84%), musculoskeletal (74%) and neurological (42%) were the most common clinical features. Disease burden was substantial, reflected by a median Paediatric Systemic Disease Index score of 3 and a mortality rate of 16%. Distinct ethnic clustering of specific gene mutations was observed. Genotype-phenotype analysis revealed that C1Q pathway defects were significantly associated with neurologic involvement, recurrent infections and anti-Sjögren's syndrome antibody A (SSA)/SSB positivity, defining a characteristic clinical profile. In contrast, DNASE1L3-related disease showed inverse associations with several clinical features, including recurrent infections, suggesting a different pathogenic and clinical trajectory. This large international cohort highlights the clinical and genetic heterogeneity of monogenic lupus. C1Q and DNASE1L3 mutations account for most cases and display distinct phenotypic profiles. These findings underscore the need for genotype-guided diagnostic and therapeutic approaches in monogenic lupus.

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2025-06-15 | Common Toll-like receptor 7 variants define disease risk and phenotypes in juvenile-onset systemic lupus erythematosus.

Toll-like receptor (TLR)7 contributes to type I interferon (IFN) expression in systemic lupus erythematosus (SLE). This study investigated genetic variability of TLR7 in 319 juvenile-onset (j)SLE patients from the UK. New generation sequencing was used to associate "common" TLR7 variants with demographic and clinical features. Three jSLE-associated variants with in silico predicted impact on gene function presented minor allele frequencies ≥5 %: rs2302267/n.-20T > G (TLR7 promoter); rs179008/p.Gln11Leu (missense variant with predicted loss-of-function); and rs3853839/c.∗881C > G (TLR7 3'UTR). The risk to develop jSLE was increased in African/Caribbean girls carrying rs3853839 GC/GG (OR: 1.8; 95 %-CI: 1.2-2.9), while the risk associated with this variant was reduced in European girls (OR: 0.5; 95 %-CI: 0.4-0.7). At inclusion, rs3853839 minor G allele carrier status associated with activity in the mucocutaneous BILAG domain (p = 0.004), "older" age at diagnosis (p = 0.003, Asian), C3 consumption (p = 0.015, boys), and higher anti-dsDNA antibody levels (p = 0.015, African/Caribbean). The negative linkage disequilibrium between rs179008 (T-C/TT) and rs3853839 (CC) associated with increased global disease activity (pBILAG-2004), and activity in the constitutional and musculoskeletal pBILAG domains. Functionally, rs2302267/n.-20T > G, may protect from leukopenia through reduced TLR7 promoter activity, while rs3853839/c.∗881C > G-3'UTR increases TLR7 mRNA stability contributing to increased gene expression. In conclusion, common TLR7 variants may influence jSLE risk and organ involvement in an ancestry-specific manner. Observations argue for genetic risk stratification and future consideration of gene variants affecting TLR7 to guide personalized treatment and care strategies.

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2025-05-19 | Trio Whole Exome Sequencing in Chinese Childhood-Onset Lupus Reveals Novel Candidate Genes.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which rare and common gene variants contribute to pathogenesis. Severe sporadic disease in children is often explained by "de novo" variants that can be uncovered by trio sequencing. Whole-exome sequencing was performed in 50 Chinese trios with childhood-onset SLE (cSLE). Rare coding variants in SLE-associated genes and all de novo variants were investigated. Gene pathway and expression analysis and interferon-β (IFNβ) luciferase assays were used to predict contribution to disease. Each proband carried at least one rare variant in an SLE-associated gene, with a median of six per child. At least two probands had monogenic disease, and one-third of probands carried novel or rare variants in genes well accepted to cause monogenic SLE: ACP5, C3, C4A, C4B, DNASE1, IFIH1, NRAS, RNASEH2B, RNASEH2C, and SAMHD1. Probands carried a median of one de novo, rare, coding variant. Intriguingly, although only two de novo variants occurred in genes previously associated with SLE, 12 of the 50 genes were enriched in the top 20 SLE-related pathways and were highly expressed in age-associated B cells and plasma B cells. These genes represent promising candidate lupus genes. Two de novo variants occurring in genes not previously linked to SLE or autoimmunity, DHX8 and ACTR5, enhanced type I IFN signaling. This study highlights the abundance of lupus-relevant rare gene variants in cSLE, supports frequent contribution of de novo variants to disease, and identifies genes that may constitute novel therapeutic targets of relevance to Chinese patients.

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