Nature Reviews Rheumatology最新文献

{"title":"Reply to ‘Is cam morphology a cause of osteoarthritis?’","authors":"Joshua Heerey, Joanne Kemp, Pim van Klij, Vasco Mascarenhas, Mark Scholes, Fleur Boel, Paul Dijkstra, Kay Crossley, Sita Bierma-Zeinstra, Rintje Agricola","doi":"10.1038/s41584-026-01374-6","DOIUrl":"10.1038/s41584-026-01374-6","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 6","pages":"404-404"},"PeriodicalIF":32.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive results for obinutuzumab in SLE phase III trial","authors":"Sarah Onuora","doi":"10.1038/s41584-026-01371-9","DOIUrl":"10.1038/s41584-026-01371-9","url":null,"abstract":"In the placebo-controlled phase III ALLEGORY trial, treatment with obinutuzumab reduced disease activity in adults with systemic lupus erythematosus over 52 weeks.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"282-282"},"PeriodicalIF":32.7,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertility, pregnancy and lactation in women with systemic lupus erythematosus","authors":"Irene E. M. Bultink, Wendy Dankers, Marjon A. de Boer, Karen Schreiber","doi":"10.1038/s41584-026-01366-6","DOIUrl":"10.1038/s41584-026-01366-6","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age. As the prevalence of SLE rises, and advances since the 1960s have substantially improved survival and quality of life, the number of women with SLE who become pregnant is steadily increasing. Although pregnancy is feasible for most patients with well-controlled SLE, pregnancy remains challenging for both women with SLE and clinicians because the risk of maternal complications and adverse fetal outcomes is higher than that in the general population. Moreover, the increased risk of pregnancy complications persists in subsequent pregnancies in women with SLE, whereas in healthy women this risk decreases owing to the development of maternal–fetal immune tolerance. During pregnancy and the postpartum period, women remain at risk of disease flares and other complications, particularly those with active disease at conception, a history of lupus nephritis, antiphospholipid syndrome or recent medication withdrawal. Important knowledge gaps persist regarding the mechanisms underlying these complications and the safety of treatment during conception, pregnancy and lactation. Preconception counselling, assessment of risk factors for adverse outcomes, pregnancy planning, timely medication adjustment and multidisciplinary management are essential to improve the maternal and fetal outcomes in women with SLE. This Review examines fertility, pregnancy and lactation in SLE, highlighting the bidirectional effects of pregnancy and disease and summarizing evidence-based approaches to counselling, risk stratification, monitoring and medication safety throughout the reproductive journey.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"302-318"},"PeriodicalIF":32.7,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147630413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germinal-centre and extrafollicular B cell pathways in systemic lupus erythematosus","authors":"Danni Yi-Dan Zhu, Carlos Castrillon, Elliot Akama-Garren, Michael C. Carroll","doi":"10.1038/s41584-026-01365-7","DOIUrl":"10.1038/s41584-026-01365-7","url":null,"abstract":"Autoantibody flares are important drivers of pathology in systemic lupus erythematosus (SLE), highlighting the pivotal role of B cells in initiating and propagating chronic autoimmunity. Although autoreactive specificities are a normal feature of the naive B cell repertoire, these cells are normally suppressed by layered tolerance checkpoints that limit inappropriate activation. Autoimmune-prone environments can lower these tolerance thresholds, rendering naive autoreactive B cells more sensitive to aberrant cues. Cytokines and other microenvironmental signals shape tissue niches that direct autoreactive B cells towards either germinal-centre or extrafollicular differentiation pathways. Germinal centres support the entry, selection and diversification of autoreactive B cells, with T cell help sustaining these repertoires. By contrast, naive autoreactive B cells entering the extrafollicular pathway exhibit an attenuated requirement for cognate T cell help and strong dependence on complement and TLR signalling. Emerging evidence continues to refine our understanding of germinal-centre and extrafollicular responses as complementary sources of autoreactive effector cells. With this progress, investigations into the origin, development, longevity and tissue dynamics of autoreactive memory B cells as chronic sources of autoantibodies are warranted. Although broad B cell depletion therapies have yielded benefit, a key challenge now is developing precision strategies that selectively target pathogenic B cell subsets. Autoreactive B cells normally held in check by tolerance checkpoints can be driven towards germinal-centre or extrafollicular differentiation in autoimmune environments. This Review examines the cellular, molecular and contextual cues that shape these pathways and considers their implications for systemic lupus erythematosus pathogenesis and therapy.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"285-301"},"PeriodicalIF":32.7,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147630412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactylation of SOD1 promotes oxidative damage in IVDD","authors":"Jessica McHugh","doi":"10.1038/s41584-026-01369-3","DOIUrl":"10.1038/s41584-026-01369-3","url":null,"abstract":"A multi-omics study reveals that lactylation of the antioxidant enzyme SOD1 promotes oxidative stress and intervertibral disc degeneration. Blocking this modification, genetically or with a targeted inhibitor, reduced oxidative damage and alleviated disc degeneration in rat models of IVDD.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"281-281"},"PeriodicalIF":32.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147599334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing vamifeport for lupus nephritis","authors":"Holly Webster","doi":"10.1038/s41584-026-01370-w","DOIUrl":"10.1038/s41584-026-01370-w","url":null,"abstract":"Preclinical findings indicate that vamifeport, an oral ferroportin inhibitor, could be used as an adjunct therapy for lupus nephritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"282-282"},"PeriodicalIF":32.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147530985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgG4 surge predicts relapse in IgG4-RD","authors":"Holly Webster","doi":"10.1038/s41584-026-01368-4","DOIUrl":"10.1038/s41584-026-01368-4","url":null,"abstract":"Findings suggest that changes in serum IgG4 levels over time are predictive of IgG4-related disease relapse and might identify patients amenable to preventative treatment.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"281-281"},"PeriodicalIF":32.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIX1 and PAI-1 emerge as therapeutic targets in systemic sclerosis","authors":"Sarah Onuora","doi":"10.1038/s41584-026-01367-5","DOIUrl":"10.1038/s41584-026-01367-5","url":null,"abstract":"Two studies highlight the potential of inhibiting the transcription factor SIX1 or its downstream mediator plasminogen activator inhibitor 1 as a strategy to limit fibrosis in systemic sclerosis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 4","pages":"218-218"},"PeriodicalIF":32.7,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodevelopmental comorbidities in juvenile systemic autoimmune and autoinflammatory diseases","authors":"Pierre Ellul, Isabelle Melki","doi":"10.1038/s41584-026-01356-8","DOIUrl":"10.1038/s41584-026-01356-8","url":null,"abstract":"Neurodevelopmental disorders affect a substantial proportion of children and represent a major public health challenge worldwide. Emerging evidence highlights complex interactions among genetic, environmental and immune factors — particularly during the critical window of neurodevelopmental vulnerability. These insights raise the possibility that children with juvenile systemic autoimmune and autoinflammatory diseases are at an increased risk of developing neurodevelopmental disorders. Early onset and delayed treatment of these autoimmune and autoinflammatory diseases seem to increase this vulnerability. Growing awareness of these associations is transforming paediatric rheumatology, highlighting the need for early screening, multidisciplinary management, and personalized interventions that target both inflammatory disease and neurodevelopment. International research collaborations, biomarker discovery and long-term follow-up are crucial for closing knowledge gaps and subsequently advancing care and outcomes. Recognizing and tackling neurodevelopmental disorders as frequent comorbidities of juvenile systemic autoimmune and autoinflammatory diseases is vital for improving educational attainment, psychosocial wellbeing and lifelong quality of life in children with chronic inflammatory conditions. Neurodevelopmental disorders frequently co-occur with juvenile systemic autoimmune and autoinflammatory diseases, driven by immune–neurodevelopmental interactions. Early screening, multidisciplinary care and personalized interventions are essential, alongside research into mechanisms, biomarkers and long-term outcomes to improve education, psychosocial wellbeing and quality of life.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"328-339"},"PeriodicalIF":32.7,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap: combining treat-to-target and difficult-to-treat strategies in the management of rheumatoid arthritis","authors":"Lilla Gunkl-Tóth, Iain B. McInnes, György Nagy","doi":"10.1038/s41584-026-01354-w","DOIUrl":"10.1038/s41584-026-01354-w","url":null,"abstract":"The treat-to-target (T2T) strategy, which involves predefined therapy objectives and a focused monitoring system, has substantially improved the management of rheumatoid arthritis (RA). These benefits probably result from a reduction in undertreatment, prevention of overtreatment and thus an improvement in long-term outcomes for both articular manifestations and comorbidities. However, T2T has also revealed a subgroup of patients who, despite following guideline-based treatment, do not reach the predefined outcomes. This finding has led to the emerging concept of ‘difficult-to-treat’ (D2T) RA. D2T-RA might reflect true pharmacological refractoriness, but D2T-RA is also increasingly recognized as having broader underlying causes, including psychosocial distress, comorbidities, chronic pain syndromes and patient or system-related barriers. If these underlying factors remain unidentified, unnecessary treatment escalation can occur, which could worsen long-term outcomes. Although T2T focuses on predefined targets and regular monitoring, which works well for the majority of patients, the structured multidomain approach characteristic of the D2T framework might provide a guide for managing patients who do not reach these targets despite guideline-based care. For this population, the D2T approach could offer better stratification and serve as a practical, precision-medicine-oriented extension of T2T by providing a more mechanism-informed, personalized management strategy. Integrating this D2T perspective into T2T practices keeps the strengths of T2T while also offering individualized care for patients with more complex disease trajectories, representing an unmet need. In this Perspective, the authors discuss how integrating difficult-to-treat into the treat-to-target strategy could improve outcomes for those patients with rheumatoid arthritis who do not follow the standard treat-to-target trajectory. The proposed strategy is aimed at providing a more personalized approach to disease management for those patients with difficult-to-treat disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 5","pages":"319-327"},"PeriodicalIF":32.7,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}