Search Results (46)

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which B-cell dysregulation plays a central pathogenic role beyond autoantibody production. Advances in B-cell biology have led to the development of targeted therapies, including inhibition of the B-cell activating factor (BAFF) pathway. Belimumab, a monoclonal antibody that neutralizes soluble BAFF, modulates B-cell survival signals upstream, promoting progressive immunologic remodeling rather than rapid depletion. This review integrates current knowledge on BAFF-dependent B-cell biology with mechanistic, pharmacokinetic, and clinical data to provide a comprehensive framework for understanding belimumab’s effects in SLE and lupus nephritis (LN). Belimumab preferentially reduces transitional and naïve B cells, while memory B cells show a relative transient increase followed by a gradual return to baseline levels, reflecting redistribution rather than expansion, and long-lived plasma cells are largely unaffected. These effects result in progressive remodeling of B-cell compartment dynamics and contribute to broader modulation of adaptive immune amplification pathways. Pharmacokinetic data support a threshold-based model of BAFF neutralization, with exposure influenced by disease-related factors such as proteinuria in LN. Clinical response is primarily determined by baseline disease biology, with greater benefit observed in patients with serologically active disease and less established organ involvement. Across clinical trials and real-world studies, belimumab reduces disease activity and flares, enables glucocorticoid tapering, and slows organ damage accrual. In LN, it improves renal outcomes and reduces the risk of kidney-related events. Collectively, these findings support belimumab as a disease-modifying therapy in SLE. Further research is needed to refine patient selection and optimize treatment sequencing and combination strategies. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of childbearing age, and active disease during pregnancy is associated with increased maternal and fetal morbidity. Belimumab is an effective biologic therapy for active SLE; however, its use during pregnancy has long been limited by the scarcity of safety data. Recent evidence and updated international recommendations suggest that belimumab may be considered in selected cases when required to maintain maternal disease control. We report the case of a woman with SLE who experienced three consecutive pregnancies with live births between 2019 and 2024 while receiving belimumab, allowing an intra-individual comparison of different exposure strategies. During the first pregnancy, belimumab was discontinued at conception and was followed by a disease flare in late pregnancy and postpartum. In the second and third pregnancies, belimumab was continued until gestational week 20 following shared decision-making with the patient; nevertheless, disease flares occurred during the third trimester of both pregnancies. All pregnancies resulted in live births at term, with no congenital anomalies, placental insufficiency, or fetal growth restriction. One neonate from the third pregnancy developed early-onset neonatal sepsis and meningitis, which resolved completely after antibiotic treatment. All children are currently growing and developing normally. This case supports a risk-adapted approach to belimumab use during pregnancy. In selected women with SLE at high risk of disease reactivation, continuation of belimumab until mid-gestation may contribute to improved maternal disease control without evident adverse fetal outcomes. Full article

Lupus nephritis (LN) stands out as one of the most critical complications of systemic lupus erythematosus (SLE), affecting almost 60% of the patient population. Even though more therapies have been made available for LN in the past decade, clinical outcomes remain less than ideal: nearly 10% to 30% of LN cases still advance to end-stage kidney disease (ESKD), still making the management of LN a clinical challenge. Therefore, the primary aim of treatment of LN is simple: to halt the progression toward chronic kidney disease (CKD) and prevent renal failure. In this review, we briefly describe the immunopathological basis of LN, which provides the scientific rationale for new drug development. We will focus on the current in-use medications, especially on proliferative LN, building on the legacy of the 20th century, and we will outline new emerging targeted and innovative therapies. We will also present the standard-of-care as informed by international guidelines and review the management of special groups, including children and pregnant women. Full article

Background: Systemic sclerosis (SSc) is a complex autoimmune fibrotic disorder marked by heterogeneous clinical features and multiple pathophysiological mechanisms. The rapid emergence of targeted therapies, aimed at selectively modulating molecular targets, has expanded treatment options; however, making direct efficacy comparisons remains challenging due to the variability in trial designs, endpoints, and patient populations. Methods: A systematic search of PubMed and ClinicalTrials.gov identified randomized controlled trials (RCTs) evaluating targeted therapies in SSc. A longitudinal mixed-effect meta-model incorporating Emax structural functions characterized treatment response trajectories for the modified Rodnan skin score (mRSS) and forced vital capacity (FVC). Between-study and between-treatment-arm variability were explicitly modeled to account for heterogeneity. Results: A total of 32 RCTs with 2036 patients and 23 targeted agents were analyzed. Guselkumab, an anti-IL-23 antibody, showed the greatest effect on mRSS, followed by tofacitinib, inebilizumab, and baricitinib. For FVC, B-cell-targeted therapies, with belimumab and rituximab, demonstrated the highest efficacy, while tocilizumab and nintedanib had more moderate effects. Time to 50% maximal response was approximately 27.5 weeks, indicating a 6.3-month period for half treatment response development. Conclusions: This model-based meta-analysis provides a broad comparison of targeted therapies in SSc, highlighting distinct efficacy patterns for skin versus lung involvement and offering hypothesis-generating insights that may support treatment selection and the design of future clinical trials. Full article

Background: Childhood-onset systemic lupus erythematosus (cSLE) is a rare, serious autoimmune disease characterized by multiorgan involvement and long-term morbidity. Although several studies have examined this condition in Japan, a comprehensive summary of recent findings remains lacking. Methods: PubMed was searched for Japanese publications on cSLE published between 2015 and 2025, including clinical studies, case reports, translational research, basic science studies, systematic reviews, clinical practice guidance, and transition care guidance. Results: Sixty publications met the inclusion criteria: 20 clinical studies, 30 case reports, 6 translational studies, 1 basic science study, 1 systematic review, 1 clinical practice guidance, and 1 transition care guidance. Most clinical studies were retrospective, although multicenter and registry-based designs have increased in recent years. Lupus nephritis remained the primary research focus, with accumulating evidence supporting mycophenolate mofetil, tacrolimus, and early belimumab as glucocorticoid (GC)-sparing approaches. Case reports illustrated the broad clinical spectrum of cSLE, with hematological and vascular complications being the most frequently reported. Translational studies highlighted the pathogenic role of type I interferon signaling and cytokine dysregulation, particularly in macrophage activation syndrome. Despite these advances, prospective studies and standardized assessment methods for pediatric-specific practice remain limited. Conclusions: Over the past decade, cSLE research in Japan has contributed to a deeper understanding of its clinical and immunological characteristics. However, treatment-related complications and long-term organ damage remain important challenges. Continued multicenter collaboration and domestic data accumulation may strengthen the evidence base, facilitate optimization of GC-sparing approaches, improve clinical management, and provide background information to support future discussions on clinical practice guidelines. Full article

Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent literature was conducted to characterize infectious complications associated with modern immunomodulatory biologic agents, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, a systematic search was performed on Scopus, Science Direct, and PubMed for studies published since 2023. Inclusion criteria focused on adult human subjects, exposure to immunomodulatory therapy, and reported infectious outcomes. Studies focusing exclusively on antineoplastic agents without established use in autoimmune diseases were excluded. After screening 1046 unique records, 16 studies were included in the final review. Findings: High-dose glucocorticoids remain a primary driver of serious infections across autoimmune diseases. Newer agents present mechanism-specific risk profiles. JAK inhibitors are associated with herpes zoster, while TNF-α inhibitors are linked to opportunistic bacterial infections and reactivation of granulomatous infections. B-cell depletion with rituximab correlates with hypogammaglobulinemia and its associated infections, whereas belimumab may offer a lower infection risk in non-renal SLE. Recent post hoc analyses (2023–2025) quantify the elevated risk of herpes zoster with JAK inhibitors compared to TNF inhibitors, particularly in older populations. Conclusions: The infectious risk associated with biologic and targeted DMARDs varies by mechanism. While glucocorticoids remain a primary driver of serious infections, newer data highlights specific vulnerabilities with JAK inhibitors (herpes zoster) and B-cell depletion (hypogammaglobulinemia) that require targeted risk stratification. This review shows the urgent need for individualized risk stratification, targeted prophylaxis (e.g., for Pneumocystis or zoster), and pre-therapy screening to balance therapeutic efficacy with patient safety. Full article

Belimumab, a human monoclonal antibody that works against B-cell activating factor (BAFF), has significantly advanced the management of systemic lupus erythematosus (SLE). Beyond the initial Phase III randomised controlled trials (RCTs) that demonstrated efficacy for belimumab as an add-on to non-biological standard therapy (ST) along with a favourable safety profile, more than 50 post hoc analyses of RCT data have provided additional insights into its clinical utility. These analyses have shown uniformly that belimumab increases the likelihood of achieving meaningful reductions in disease activity, sustained low disease activity, and improved health-related quality of life (HRQoL) outcomes, with more pronounced benefits in serologically active SLE. Studies focusing on organ-specific manifestations revealed that belimumab confers benefits across multiple SLE facets, with prominent effects on musculoskeletal and mucocutaneous symptoms. Along the same lines, post hoc analyses of the BLISS-LN trial demonstrated benefit from belimumab regarding multiple renal outcomes, including reduced renal flare rates, improved glomerular filtration rate, and improved histological findings in repeat kidney biopsies. Long-term extension studies and real-world evidence confirm its durable efficacy and safety, with continued reductions in overall disease activity, glucocorticoid use, and healthcare resource utilisation over several years. By exploring different efficacy endpoints, person-centred outcomes, disease trajectories, and characteristics across organ manifestations, this body of post-marketing evidence has not only enhanced our understanding of belimumab use in SLE but also constitutes a comprehensive framework for future clinical trial design and development of novel therapeutic strategies. The present review summarises key findings of post hoc analyses of RCTs and observational studies of belimumab. Full article

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder in which ocular involvement represents a clinically significant yet frequently underrecognized contributor to morbidity. Ocular manifestations in SLE may arise from disease activity itself, but also as adverse effects of long-term pharmacological therapy. With the advent of targeted immunomodulatory agents, the therapeutic landscape of SLE has expanded beyond conventional drugs such as hydroxychloroquine and corticosteroids toward biologics and small molecules designed to interfere with specific immunological pathways. These advances have improved systemic disease control and survival; however, their ophthalmological safety profiles remain only partially defined. This review synthesizes current evidence on ocular adverse events associated with both traditional and emerging SLE therapies. Established agents, particularly hydroxychloroquine and corticosteroids, are consistently linked to complications including retinopathy, posterior subcapsular cataracts, steroid-induced glaucoma, and central serous chorioretinopathy. In contrast, recently approved or investigational therapies—such as belimumab, anifrolumab, voclosporin, dual BAFF/APRIL inhibitors, rituximab, JAK inhibitors, CD40/CD40L blockade, CD38 inhibition, and mesenchymal stromal cell-based strategies—have limited but evolving safety data, with potential ocular adverse events spanning inflammatory, vascular, neuro-ophthalmic, and structural domains. Although ocular complications appear infrequent in clinical trials, underdetection in real-world practice and insufficient long-term monitoring may underestimate their true incidence. These findings highlight the need for systematic ophthalmological surveillance in patients receiving immunomodulatory therapies for SLE. Early recognition and timely management of ocular toxicity are crucial to safeguarding visual function and optimizing long-term therapeutic outcomes in this vulnerable patient population. Full article

Belimumab, a fully humanized B cell-activating factor (BAFF)-targeting monoclonal antibody, inhibits autoreactive B cell survival and improves systemic lupus erythematosus (SLE) clinical outcomes. However, its administration criteria remain unclear. To establish a basis for defining these criteria, we characterized the immune cell subpopulation alterations post-belimumab treatment and elucidated the underlying mechanisms. We hypothesized that belimumab modulates specific cell subsets and investigated the post-therapy changes. Flow cytometry and correlation analysis revealed that the frequency of B- and T-lymphocyte attenuator (BTLA)^high memory B cells in peripheral blood and clinical improvement after belimumab treatment. Western blotting analysis of healthy control B cells revealed that BTLA engagement suppressed Bruton tyrosine kinase and phospholipase C-gamma 2 phosphorylation, which was enhanced by B cell and BAFF receptor co-stimulation. BTLA-expressing memory B cells, which positively correlate with disease improvement, possibly contributed to SLE improvement via BTLA-mediated signaling that attenuated B cell- and BAFF receptor-induced intracellular pathways. To validate these findings, we plan to further assess the effects of belimumab on BTLA expression and B cell signaling pathways in treatment-naive patients with SLE by western blotting. Collectively, our results provide a novel foundation for establish appropriate belimumab administration criteria. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs and the production of anti-double-stranded DNA (anti-dsDNA) antibodies. This study evaluated the associations between anti-dsDNA levels and smoking, oral corticosteroid (OCS) use, and immunosuppressive therapy in SLE patients. A retrospective monocentric analysis was performed on 119 SLE patients. Data on smoking history, OCS dosage, and immunosuppressive treatments were collected. Anti-dsDNA levels were assessed using fluorescent enzyme immunoassays and confirmed via indirect immunofluorescence. Smoking was significantly associated with higher anti-dsDNA levels (Spearman’s ρ = 0.292, p = 0.0014). Logistic regression identified pack-years (PPY) as a predictor of high anti-dsDNA levels (≥75 U/mL), with a 50% probability at 12.51 PPY and a 75% probability at 17.65 PPY (p < 0.001). OCSs were used by 58.82% of patients, with a median prednisone-equivalent dose of 5.0 mg; higher OCS doses correlated weakly but significantly with anti-dsDNA levels (R² = 0.066, p < 0.001). Anti-dsDNA levels differed across treatments (p = 0.027): MTX vs. AZA/MMF, and belimumab vs. AZA/MTX. Smoking, OCS use, and immunosuppressants influence anti-dsDNA levels. Belimumab showed greater reduction compared to conventional therapies. Personalized treatment strategies are needed, considering the effects of smoking and cortico-steroids. Full article

Introduction: Gut dysbiosis has been associated with the development of autoimmune diseases, including systemic lupus erythematosus (SLE). Although previous studies suggest microbial alterations in SLE, evidence at the species level and its clinical relevance remain limited. This study aimed to characterise the gut microbiota at species level in SLE patients and evaluate its association with clinical features. Materials and methods: A total of 57 SLE patients and 57 matched controls were included. Faecal samples were collected using the OMNIgene-GUT kit, and microbial DNA was extracted with the Maxwell RSC PureFood GMO kit. Metagenomic sequencing was performed using the Illumina MiSeq platform, and the data was analysed with QIIME2. Microbial diversity and relative abundance were assessed using the phyloseq package, and differentially abundant taxa were identified using DESeq2. Clinical subgroups among SLE patients were identified via k-means clustering. Results: SLE patients exhibited significantly different beta diversity compared to controls (p = 0.001), with increased abundance of Pseudomonadota (3.81% vs. 6.80%, p < 0.05) and decreased Bacteroidota (53.42% vs. 38.04%, p < 0.05). Only 10 bacterial species were consistently present across all SLE samples, including Akkermansia muciniphila, Bacteroides dorei, and Lactobacillus gasseri. Hypertensive patients and those treated with corticosteroids presented a marked depletion of key microbial taxa. Conversely, Belimumab-treated patients displayed a distinct microbiota enriched in species such as Alistipes shahii and Prevotella corporis. Conclusions: This study confirms significant gut microbiota alterations in SLE and pinpoints microbial profiles associated with clinical subgroups. These findings suggest gut dysbiosis may contribute to SLE pathogenesis and indicate biomarkers for disease stratification. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse clinical manifestations that can lead to severe organ damage. The complex pathophysiology of SLE makes treatment selection difficult. This review examines the current evidence for biological therapies in SLE, including the anti-B cell activating factor antibody belimumab; the type I interferon receptor antagonist anifrolumab; the novel calcineurin inhibitor voclosporin; and rituximab, which targets CD20 on B cells. We also describe emerging therapies, including novel agents in development and CD19-directed chimeric antigen receptor (CAR) T cell therapy, which has shown promise in early clinical experience. Recent advances in biomarker research, including interferon signatures and transcriptomic profiles, may facilitate patient stratification and treatment selection. This review offers insights into current and future treatment strategies for patients with SLE by analyzing clinical trial results and recent immunological findings. Full article

Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus, affecting roughly 40% of all lupus patients. With the introduction of cyclophosphamide and mycophenolate mofetil, outcomes have dramatically improved. However, 10% of patients still progress towards end-stage kidney disease, which carries an elevated mortality rate. In recent years, several novel agents have been approved for use or have shown preliminary evidence of efficacy in lupus nephritis. These agents include belimumab, voclosporin, and obinutuzumab, among others. Efficacy has also been demonstrated in recent trials combining older drugs. However, determining which patients would benefit the most from novel agents or combined drug regimens and whether these drugs might serve as an alternative to current remission-induction drug regimens rather than as add-on therapies remain unresolved issues. In this review, we will explore the current evidence regarding the efficacy of novel agents. Full article

The BAFF-APRIL system is crucial for the pathogenesis of systemic lupus erythematosus (SLE) by promoting B cell survival, differentiation and the maintenance of humoral autoimmunity. Here, we investigated the relationship of BCMA expression on B cell subsets with its ligands BAFF and APRIL, together with soluble BCMA, and with clinical and serologic variables in a cohort of 100 SLE patients (86 under conventional and 14 under belimumab therapy) and 30 healthy controls (HCs) using multicolor flow cytometry and ELISA. We found that BCMA expression in SLE patients was significantly increased on all B cell subsets compared to HCs, with all examined components of the BAFF-APRIL system being upregulated. BCMA expression was significantly increased on switched and unswitched memory B cells compared to naïve B cells, both in HCs and SLE. BCMA expression on B cells correlated with plasmablast frequencies, serum anti-dsDNA antibodies and complement consumption, while soluble BCMA correlated with plasmablast frequency, highlighting its potential as a clinical biomarker. Belimumab treatment significantly reduced BCMA expression on most B cell subsets and soluble TACI and contributed to the inhibition of almost the entire BAFF-APRIL system and restoration of B cell homeostasis. These results provide insights into the complex dysregulation of the BAFF-APRIL system in SLE and highlight the therapeutic potential of targeting its components, particularly BCMA, in addition to its use as a biomarker for disease activity. Full article

Introduction: Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by significant autoantibodies, particularly targeting nuclear antigens. SLE pathogenesis involves genetic, environmental, and hormonal factors. The disease course includes flares and remission and involves various organs. Recent therapeutic progresses, including biologics, have improved management and prognosis, though the long-term impact of novel therapies remains to be determined. Biologics in SLE: Rituximab, the earliest B-cell-oriented biologic, binds CD20 and depletes CD20+ B cells, leading to remission in some SLE patients. Belimumab is a B-cell-activating factor (BAFF) inhibitor with a recent additional indication for lupus nephritis. The CALIBRATE and BLISS-BELIEVE studies investigated combinations of these drugs with conventional therapies, showing varied efficacy. Ocrelizumab and obinutuzumab, newer CD20-oriented SLE therapies, together with ofatumumab and veltuzumab, are also promising. The latest trials highlight their efficacy and safety. Anifrolumab, targeting type-I interferon receptors, was evaluated in the TULIP 1/2 trials. The ongoing TULIP LTE trial supports the long-term safety and efficacy of anifrolumab. Additionally, the IRIS Phase III trial is exploring anifrolumab for lupus nephritis, showing favorable renal responses. Tocilizumab and secukinumab are being assessed for SLE, with mixed outcomes. Several biologics targeting the C5 complement protein, together with immunomodulators and immunotherapeutics, are also under investigation for potential benefits in SLE. Discussion: Biologics in SLE target specific immune components, aiming to improve disease control and reduce the side effects of conventional therapy. However, trial outcomes vary due to factors like inclusion criteria and trial design. Conclusions: Biotechnology progress enables targeted biologic therapies for SLE, reducing disease activity and improving patients’ quality of life. Full article