Journal of autoimmunity最新文献

{"title":"Anti-MDA5 monoclonal antibodies from patients with dermatomyositis – B cell characteristics and differential targeting of the helicase domains","authors":"Eveline Van Gompel ,&nbsp;Marina Galešić ,&nbsp;Nicolas Delaroque ,&nbsp;Karolin Kern ,&nbsp;Ragnhild Stålesen ,&nbsp;Antonella Notarnicola ,&nbsp;Deniz Demirdal ,&nbsp;Monika Hansson ,&nbsp;Annika van Vollenhoven ,&nbsp;Edvard Wigren ,&nbsp;Susanne Gräslund ,&nbsp;Michael Szardenings ,&nbsp;Vivianne Malmström ,&nbsp;Ingrid E. Lundberg ,&nbsp;Begum Horuluoglu ,&nbsp;Caroline Grönwall ,&nbsp;Karine Chemin ,&nbsp;Vijay Joshua","doi":"10.1016/j.jaut.2026.103536","DOIUrl":"10.1016/j.jaut.2026.103536","url":null,"abstract":"<div><h3>Objectives</h3><div>Autoantibodies targeting melanoma differentiation associated protein 5 (MDA5) are strongly associated with dermatomyositis (DM) and may contribute to its pathogenesis. Here we aimed to investigate MDA5⁺ B cells, their phenotype and generate MDA5 monoclonal antibodies to assess their epitope specificity.</div></div><div><h3>Methods</h3><div>MDA5-reactive B cells were captured from peripheral blood of patients with anti-MDA5⁺ DM (n = 3) using an MDA5-fluorescent probe. B cell receptor (BCR) sequences were analysed from single-sorted B cells (n = 240). Selected clones were re-expressed as IgG1 monoclonal antibodies (mAbs, n = 23). Reactivity was assessed using recombinant MDA5 protein constructs, peptide epitope mapping, ELISA, western blot and a commercial line blot assay.</div></div><div><h3>Results</h3><div>Of 240 anti-MDA5⁺ sorted B cells, 23 BCRs were re-expressed as mAbs, two of which showed high reactivity and specificity for MDA5. These antibody sequences originated from one CD19⁺IgD⁻CD27⁻CD38⁺ and one CD19⁺IgD⁻CD27⁺CD38⁺ IgG⁺ B cell with low somatic hypermutation (SHM). Both mAbs had nanomolar apparent affinity and bound to sites within the helicase domains of the MDA5 protein but with distinct epitope recognition. Serology screening confirmed targeting of a linear epitope identified in the mAb studies.</div></div><div><h3>Conclusion</h3><div>Our results show that anti-MDA5⁺ B cells recognize the helicase domains, which are the enzymatically active domains of the protein. These results have implications for understanding the etiopathology of anti-MDA5⁺ DM and development of new antigen-specific therapies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103536"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258238","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":"What's in a name? – juxtaposing T follicular, peripheral and resident helper cells in B cell-driven autoimmune diseases","authors":"Fabiënne van Puijfelik ,&nbsp;Kirsten L. Kuiper ,&nbsp;Jasper Rip ,&nbsp;Joost Smolders ,&nbsp;Marvin M. van Luijn","doi":"10.1016/j.jaut.2026.103535","DOIUrl":"10.1016/j.jaut.2026.103535","url":null,"abstract":"<div><div>Effective humoral immunity depends on tightly regulated interactions between B cells and CD4⁺ T-helper subsets across lymphoid and peripheral tissues. In autoimmune diseases, these regulatory checkpoints fail, enabling autoreactive B cells to mature, infiltrate tissues and/or produce pathogenic autoantibodies. Three major CD4⁺ helper subsets, T follicular helper (T_FH), T peripheral helper (T_PH), and tissue-resident memory (T_RM) cells, play key roles in shaping these responses. T_FH cells are defined by CXCR5, PD-1 and BCL6 expression and orchestrate germinal centre (GC) reactions in secondary lymphoid organs (SLOs). T_PH cells are part of tertiary lymphoid structures (TLS) and provide potent help to memory and atypical B cells and drive antibody-secreting cell formation within inflamed tissues in autoimmune diseases. CD4⁺ T_RM cells are imprinted by local cues to acquire tissue residency programs characterized by CD69 and CD103. Although not exclusively related to B-cell help, their effector function is key for preventing tissue inflammation, including the onset of organ-specific autoimmune diseases. Notably, CD4⁺ T_RM cells share transcriptional programs with T_PH cells as well as circulating precursor T helper subsets such as Th17.1 cells. Understanding the shared and divergent transcriptional, migratory and functional programs of these helper subsets is essential for defining how tissue contexts stimulate pathogenic rather than protective B-cell responses in autoimmunity.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103535"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113100","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":"Interventional studies targeting the prodromal or preclinical phase of immune-mediated disease to benefit patient outcomes: a scoping review","authors":"Kara Moscovitz ,&nbsp;Daivat Bhavsar ,&nbsp;Helen Tremlett","doi":"10.1016/j.jaut.2026.103526","DOIUrl":"10.1016/j.jaut.2026.103526","url":null,"abstract":"<div><h3>Background</h3><div>Immune-mediated diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1D) often progress through prodromal or preclinical phases before classical symptom onset. These early stages present opportunity for preventative interventions, but evidence on their efficacy and safety has not been systematically synthesized.</div></div><div><h3>Objective</h3><div>This scoping review evaluated interventional studies targeting the prodromal/preclinical phases of MS, RA, SLE, and T1D, with a focus on efficacy and safety outcomes.</div></div><div><h3>Methods</h3><div>We systematically searched MEDLINE, EMBASE, and Web of Science for interventional studies published between January 2010 to June 2024. Studies assessing any intervention in individuals during the early phases of MS, RA, T1D, or SLE were included.</div></div><div><h3>Results</h3><div>Of 1455 screened studies, 23 met inclusion criteria: 13 for RA, 8 T1D, 2 MS, and none for SLE. For RA, abatacept lowered risk of disease onset in some trials (hazard ratio [HR] range = 0.14–0.61), while methotrexate and rituximab showed modest or subgroup-specific benefit. For T1D, teplizumab delayed clinical onset by over two years (median), preserved β-cell function and lowered risk of progression to T1D (adjusted HR = 0.41; 95% CI 0.22–0.78). For MS, teriflunomide (aHR = 0.28; 95% CI 0.11–0.71) and dimethyl fumarate (aHR = 0.07; 95% CI 0.01–0.45) lowered risk of clinical conversion in persons with radiologically isolated syndrome. Interventions demonstrated expected safety profiles.</div></div><div><h3>Conclusion</h3><div>Interventions targeting preclinical or prodromal phases of immune-mediated diseases can delay clinical onset, particularly in RA, T1D, and MS. Progress will require harmonized preclinical definitions, improved risk stratification, longer follow-up, and dedicated efforts in underrepresented diseases such as SLE.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103526"},"PeriodicalIF":7.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025595","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":"Immune cell-derived cytokines synergistically interact to drive synovial fibroblast invasive function and metabolic capacity","authors":"Órla Tynan ,&nbsp;Alyssa Gilmore ,&nbsp;Aenea A.I. Brugman ,&nbsp;Achilleas Floudas ,&nbsp;Conor M. Smith ,&nbsp;Dumitru Anton ,&nbsp;Siobhán Wade ,&nbsp;Carl Orr ,&nbsp;Douglas J. Veale ,&nbsp;Ursula Fearon","doi":"10.1016/j.jaut.2025.103519","DOIUrl":"10.1016/j.jaut.2025.103519","url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is a chronic autoimmune disease, defined by synovial inflammation and joint destruction. A significant proportion of patients still have sub-optimal/no response to current treatments, with recent synovial scRNA-seq studies highlighting the complexity of the inflamed joint. This study investigates synovial-scRNA-seq predicted IL-1β/TGF-β synergistic regulation of RA synovial-fibroblast (FLS) pathogenic function. Synovial bulk RNA-seq analysis demonstrated increased expression of IL-1β and TGF-β signalling components in healthy controls (HC) versus early RA versus established RA, with synovial scRNA-seq demonstrating enrichment in specific RA-FLS clusters. In RA-FLS, IL-1β/TGF-β synergistically increased baseline glycolysis, ECAR:OCR ratio, proton-efflux rate, %PER glycolysis, compensatory glycolysis, and glycolytic genes (GLUT-1, PKM2, PFKFB3). Synergistic dysregulation of mitochondrial function (biogenesis and DRP1 fission protein) and endoplasmic reticulum (ER) stress responses (ER size, stress genes, chaperone protein (PDI)) were also demonstrated. The altered metabolic profile was paralleled by synergistic induction of pro-inflammatory mediators/chemokines including IL-8, MCP-1, MMP-3, and CXCL5 in RA-FLS. IL-1β and non-canonical TGF-β signalling converge on TAK1 activation. Takinib (TAK1-inhibitor) significantly reduced glycolytic and pro-inflammatory responses of RA-FLS. Importantly, in RA <em>ex vivo</em> synovial explants (reflecting the inflamed joint), Takinib reduced spontaneous release of pro-inflammatory mediators and the process of synovial growth. In conclusion, IL-1β/TGF-β synergistically drive a pathogenic RA-FLS phenotype in RA, blockade of which reduces inflammatory and invasive mechanisms.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103519"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819452","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":"Autoimmunity to mental health: Risk of depression in type 1 diabetes and celiac disease patients – A systematic review, meta-analysis, and bias assessment","authors":"Dagem Desalegn ,&nbsp;Simone Fischer ,&nbsp;Yeabsira Bedada ,&nbsp;Dennis Freuer ,&nbsp;Christa Meisinger","doi":"10.1016/j.jaut.2026.103524","DOIUrl":"10.1016/j.jaut.2026.103524","url":null,"abstract":"<div><h3>Background</h3><div>Depression is expected to become the world's largest disease burden by 2030. However, the incidence of depression in individuals with Type 1 diabetes mellitus (T1DM) or Celiac disease (CD) remains poorly studied. To address this gap, a systematic review and meta-analysis was carried out.</div></div><div><h3>Methods</h3><div>This systematic review was approved at PROSPERO on February 9, 2025, and followed the PRISMA and MOOSE guidelines. The literature search considered all peer-reviewed quantitative studies from relevant databases up to February 7, 2025. Study-specific risk of bias was assessed using the ROBINS-E tool. Inverse variance weighted random-effects models were applied on the hazard ratio (HR) scale to pool estimates of included studies. Heterogeneity was quantified by Cochran's <em>Q</em> and <span><math><mrow><msup><mi>I</mi><mn>2</mn></msup></mrow></math></span> statistics. Sensitivity analyses consisted of influence, outlier, and subgroup analyses. E-values were calculated to assess the reliability of results regarding unmeasured confounding.</div></div><div><h3>Results</h3><div>Out of 17,095 articles screened, eight studies for T1DM and two for CD were included in the study. Both T1DM (HR = 2.77; 95 % CI: [1.82; 4.21]; P &lt; 0.0001; <span><math><mrow><msup><mi>I</mi><mn>2</mn></msup></mrow></math></span> = 98.5 %) and CD (HR = 1.66; 95 % CI: [1.51; 1.84]; P &lt; 0.0001; <span><math><mrow><msup><mi>I</mi><mn>2</mn></msup></mrow></math></span> = 35.3 %) were consistently associated with the onset of depression. Despite the high heterogeneity, which could not be fully explained for T1DM, the sensitivity analyses confirmed the results, while the E-values underscored their robustness against unmeasured confounding.</div></div><div><h3>Conclusions</h3><div>This meta-analysis indicates a significant increase in the incidence of depression in individuals with either T1DM or CD. Depression screening for these population is recommended. Further research is needed to clarify the underlying mechanisms for these associations.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103524"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976759","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":"Proinflammatory CD20+CD3+ T cells as a potential driver of macrophage reprogramming in rheumatoid arthritis","authors":"Suna Jiang ,&nbsp;Jiawei Xue ,&nbsp;Haonan Jia ,&nbsp;Maolin Chu ,&nbsp;Yeye Ma ,&nbsp;Haihong Zhang ,&nbsp;Wenjing Li ,&nbsp;Changju Li ,&nbsp;Yanli Wang ,&nbsp;Hongying Li ,&nbsp;Juan Zhang","doi":"10.1016/j.jaut.2025.103515","DOIUrl":"10.1016/j.jaut.2025.103515","url":null,"abstract":"<div><h3>Objective</h3><div>CD20⁺CD3⁺ T cells, a distinct immune cell population implicated in immune responses, contribute to the development of multiple diseases. However, their role in RA progression, particularly their potential to drive the reprogramming of monocyte-derived macrophages toward a pathogenic state akin to synovial tissue macrophages (STMs), remains unclear.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing and flow cytometry were conducted on RA patients and healthy controls. CD14⁺ monocytes isolated from the peripheral blood of RA patients were co-cultured with CD20⁺CD3⁺ T cells to study their effect on monocyte differentiation. A collagen-induced arthritis (CIA) model was used to assess the pathogenic potential of transferring CD20⁺CD3⁺ T cells.</div></div><div><h3>Results</h3><div>RA patients have a higher frequency of CD20⁺CD3⁺ T cells than healthy controls, with single-cell analysis showing increased ANXA1-FPR1 interaction between these T cells and monocytes. ANXA1⁺CD20⁺CD3⁺ T cells and FPR1⁺ monocytes are more prevalent in RA patients. The role of ANXA1-FPR1 signaling is supported by a higher number of CD48⁺ cells in the MerTK‾CD206‾ macrophages subset after co-culture with CD20⁺CD3⁺ T cells. CIA mice administered CD20⁺CD3⁺ T cells exhibited more severe arthritis and more proinflammatory STMs infiltration than CIA controls.</div></div><div><h3>Conclusions</h3><div>CD20⁺CD3⁺ T cells exacerbate synovitis and drive RA progression by promoting the recruitment and pro-inflammatory differentiation of monocyte-derived macrophages (particularly the CD48⁺MerTK‾CD206‾ subset) via ANXA1-FPR1 signaling, representing a potential therapeutic target.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103515"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781384","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":"Sera from patients with dermatomyositis and antisynthetase syndrome mediate muscle weakness, impair mitochondrial respiration and induce local cytokine production in muscle tissue","authors":"Cecilia Leijding ,&nbsp;Stefano Gastaldello ,&nbsp;Tomas Schiffer ,&nbsp;Suchada Kaewin ,&nbsp;Kristofer M. Andreasson ,&nbsp;Yi Zhong ,&nbsp;Begum Horuluoglu ,&nbsp;Maryam Dastmalchi ,&nbsp;Antonella Notarnicola ,&nbsp;Angeles S. Galindo-Feria ,&nbsp;Volker M. Lauschke ,&nbsp;Mattias Carlström ,&nbsp;Helene Alexanderson ,&nbsp;Ingrid E. Lundberg ,&nbsp;Daniel C. Andersson","doi":"10.1016/j.jaut.2025.103522","DOIUrl":"10.1016/j.jaut.2025.103522","url":null,"abstract":"<div><h3>Objectives</h3><div>Idiopathic inflammatory myopathies (IIM) are systemic autoimmune disorders characterized by skeletal muscle weakness and inflammatory cell infiltrates in muscle tissue. Although circulating systemic factors have been implicated in IIM, it is unclear to what extent such factors shape the muscle disease phenotype. Using a model that can isolate the effect of serum from other systemic influences, we aimed to investigate how serum from IIM affects skeletal muscle contractility, mitochondrial function and inflammatory signalling.</div></div><div><h3>Methods</h3><div>Isolated skeletal muscles (<em>m. flexor digitorum brevis</em>) from C57BL/6JRj mice were exposed for 24 h to sera from patients with IIM (<em>n</em> = 11) or healthy control sera. Muscle force was measured before and after serum exposure to assess weakness. Gene and protein expression was analysed to assess mitochondrial biogenesis and inflammatory cytokines. Mitochondrial respiration was assessed by high-resolution respirometry. Muscle transcriptomics was performed to identify signalling pathways perturbed by the IIM sera.</div></div><div><h3>Results</h3><div>Muscles exposed to sera from patients with IIM displayed significant contractile weakness and impaired mitochondrial respiratory capacity compared to muscles exposed to control sera (complex I; <em>p</em> = 0.0004, complex II; <em>p</em> = 0.0254, maximal electron transport chain activity; <em>p</em> = 0.0012). IIM sera induced upregulation of TNF-α (<em>p</em> = &lt;0.0001) and IL1β (<em>p</em> = 0.0002) in the isolated muscles. Transcriptomics revealed significant enrichment in pathways linked to inflammation, mitochondrial metabolism and cytokine activity.</div></div><div><h3>Conclusions</h3><div>Serum from patients with IIM induced disease relevant phenotypes like those observed in muscle of patients, including weakness, local cytokine expression and mitochondrial dysfunction. These findings support the relevance of our model in recapitulating key features of IIM and further the mechanistic insights.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103522"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920853","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":"Vasculopathy and vasculitis associated with levamisole-adulterated cocaine: a systematic review","authors":"Martin Scoglio ,&nbsp;Corinne Orlando ,&nbsp;Gregorio P. Milani ,&nbsp;Mario G. Bianchetti ,&nbsp;Gabriel Bronz ,&nbsp;Mattia Rizzi ,&nbsp;Sebastiano A.G. Lava ,&nbsp;Benedetta Terziroli Beretta-Piccoli ,&nbsp;Helmut Beltraminelli ,&nbsp;Marcel M. Bergmann","doi":"10.1016/j.jaut.2025.103505","DOIUrl":"10.1016/j.jaut.2025.103505","url":null,"abstract":"<div><h3>Objective</h3><div>Levamisole, once used as anthelminthic or immunomodulator, is now a common cocaine adulterant. It is linked to a systemic vasculopathy/vasculitis. Our purpose was to review its clinical, serological, and histopathological features.</div></div><div><h3>Methods</h3><div>We conducted a registered systematic review (CRD42024558898) across three databases, without language or date restrictions. Reports documenting a vasculopathy/vasculitis temporally associated with levamisole — either prescribed or as a cocaine adulterant — were included.</div></div><div><h3>Results</h3><div>172 reports describing 302 patients were included. Most cases (N = 282; 93 %) involved cocaine adulterated with levamisole. The skin was involved in 274 (91 %) and the kidney in 64 (21 %) cases. Purpura (228; 83 %) and necrosis (141; 51 %) were the most common skin lesions, predominantly affecting ears and extremities. Among 186 classifiable skin biopsies, a thrombotic vasculopathy was detected in 65, a leukocytoclastic vasculitis in 52, and both a thrombotic vasculopathy and a vasculitis in 70 cases. Among 37 renal biopsies, a pauci-immune crescentic glomerulonephritis and a membranous nephropathy were the most detected features. Leukopenia occurred in 100 (33 %) cases. Among tested cases, anti-neutrophil cytoplasmic antibodies were detected in about 89 % of cases, mostly with a perinuclear (71 %) or an atypical (25 %) pattern. Antibodies targeting the myeloperoxidase were detected in 73 % of the cases. In patients receiving levamisole for therapeutic purposes, the vasculopathy resolved after levamisole withdrawal. A relapse of the vasculopathy was observed after re-exposed to levamisole.</div></div><div><h3>Conclusions</h3><div>Levamisole-induced vasculopathy/vasculitis is a distinctive skin-predominant condition with characteristic clinical and serological features. Withdrawal of levamisole is the cornerstone of management.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103505"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661384","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":"Circadian clock genes: Potential therapeutic targets for autoimmune diseases","authors":"Tian Tian ,&nbsp;Lulu Rao ,&nbsp;Mengzhu Wei ,&nbsp;Jia Du ,&nbsp;Yiyue Gu ,&nbsp;Xiaoyan Wu ,&nbsp;Yang Ma","doi":"10.1016/j.jaut.2025.103516","DOIUrl":"10.1016/j.jaut.2025.103516","url":null,"abstract":"<div><div>Circadian rhythms are endogenous 24-h oscillations in physiological processes, with their regulation dependent on a molecular network comprising the core clock genes (<em>CLOCK, BMAL1, PER, CRY</em>) and other key clock genes (<em>NR1D1/2, RORs</em>). Research indicates that circadian rhythm disruption is a significant risk factor for immune dysregulation, while maintaining circadian rhythm balance may offer new therapeutic avenues for autoimmune diseases. This review systematically examines the regulatory mechanisms of the circadian clock genes in innate immunity, adaptive immunity (particularly Th17 cell differentiation and function), and inflammatory responses. By elucidating their molecular interactions, it clarifies the pivotal role of these clock genes in autoimmune diseases. Additionally, we have summarized research progress on small molecule modulators targeting clock genes, as well as non-pharmacological interventions such as sleep regulation, intermittent fasting (IF)/time-restricted feeding (TRF), and melatonin supplementation.In summary, this review aims to elucidate the role of clock genes in immune regulation and inflammatory responses, emphasizing their potential as therapeutic targets for autoimmune diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103516"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781365","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":"Humoral correlates of clinical response to thymectomy in myasthenia gravis","authors":"Carla D.F. Sousa ,&nbsp;Paula Terroba-Navajas ,&nbsp;John Tzartos ,&nbsp;Ivana D. Orešković ,&nbsp;Maja Pučić-Baković ,&nbsp;Gordan Lauc ,&nbsp;Yannic C. Bartsch ,&nbsp;Henry J. Kaminski ,&nbsp;Jan D. Lünemann","doi":"10.1016/j.jaut.2025.103517","DOIUrl":"10.1016/j.jaut.2025.103517","url":null,"abstract":"<div><div>Mechanisms by which thymectomy confers its clinical benefit in patients with AChR-antibody (Ab) positive myasthenia gravis (MG) remain poorly understood. We used a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to identify Ab-features that track with clinical response to thymectomy in 78 patients with AChR-Ab positive MG, recruited during the MGTX trial, an NIH-sponsored randomized, controlled study of thymectomy plus prednisone versus prednisone alone. Clinically meaningful improvement was defined as a change of at least 3 points on the quantitative MG scale at month 36 compared to baseline. AChR-specific immunoglobulin G (IgG) titers decreased in patients experiencing clinical improvement but remained stable in patients with poor response to therapy. Thymectomized patients showed an accelerated decline in AChR-specific IgG titers. At month 36, the frequency of digalactosylated and monosialylated total IgG Fc-glycans was increased in thymectomized responders compared to non-responders. Fc-glycosylation profiles were unchanged in prednisone only treated patients with or without clinically meaningful improvement. Clinical benefit achieved by thymectomy is strongly associated with an anti-inflammatory IgG Fc-glycosylation profile.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103517"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781379","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}