Journal of autoimmunity最新文献

{"title":"Vascular effects of achieving low disease activity in axial spondyloarthritis - A 2-year prospective treat-to-target study.","authors":"Huan Meng, Sze-Lok Lau, Isaac T Cheng, Vivien Pw Chan, Shirley K Ying, Jolly M Lee, Violet K Lee, Kitty Y Kwok, Isaac C Yim, Jack J Lee, Cheuk-Chun Szeto, Bryan P Yan, Alex P Lee, Ho So, Lai-Shan Tam","doi":"10.1016/j.jaut.2026.103534","DOIUrl":"https://doi.org/10.1016/j.jaut.2026.103534","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of achieving Axial Spondyloarthritis Disease Activity Score (ASDAS) low disease activity (LDA) on the progression of subclinical atherosclerosis and arterial stiffness in axial spondyloarthritis (axSpA) patients.</p><p><strong>Methods: </strong>Ninety-nine axSpA patients underwent 2 years of tight-control treatment aiming at ASDAS LDA (<2.1). Carotid intima-media thickness (cIMT) was measured using high-resolution ultrasound. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV) and augmentation index (AIx). The primary outcome was the effect of achieving LDA at 12 months (LDA group) on the progression of subclinical atherosclerosis over 24 months. Secondary outcomes included: (1) arterial stiffness progression between LDA and non-LDA groups; (2) subclinical atherosclerosis and arterial stiffness markers between patients who achieved sustained LDA (sLDA) from 12 to 24 months, and the non-sLDA groups over 24 months.</p><p><strong>Results: </strong>Ninety axSpA patients (mean age: 39 ± 10 years, 81.1% male) were included. At 12 months, 74.4% (n = 67) achieved LDA, while 50.0% (n = 45) attained sLDA at 24 months. Multivariate analysis showed achieving LDA at 12 months reduced carotid plaque progression (OR 0.27, 95% CI 0.08-0.95, P = 0.042), while achieving sLDA was associated with less progression in the total plaque area (RR -1.97, 95% CI -3.83 to -0.12, P = 0.038) over 24 months. The changes in cIMT and arterial stiffness between patents who did or did not achieve LDA/sLDA were similar.</p><p><strong>Conclusions: </strong>Effective suppression of inflammation in axSpA patients achieving LDA may be associated with a reduction in subclinical atherosclerosis progression.</p>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"103534"},"PeriodicalIF":7.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131739","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, Kirsten L Kuiper, Jasper Rip, Joost Smolders, Marvin M van Luijn","doi":"10.1016/j.jaut.2026.103535","DOIUrl":"https://doi.org/10.1016/j.jaut.2026.103535","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"103535"},"PeriodicalIF":7.0,"publicationDate":"2026-02-02","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":"2026-01-23","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":"Molecular stratification and transcriptome-guided therapeutics in systemic lupus erythematosus with insufficient treatment response","authors":"Lorenzo Beretta ,&nbsp;Chiu Wai Shirley Chan ,&nbsp;Georgia-Savina Moysidou ,&nbsp;Danae-Mona Nöthling ,&nbsp;Alexandra Ainatzoglou ,&nbsp;Andrea Zoli ,&nbsp;Spyridon Katechis ,&nbsp;Antonis Fanouriakis ,&nbsp;Aline Bozec ,&nbsp;Prodromos Sidiropoulos ,&nbsp;Christina Bergmann ,&nbsp;Dimitrios T. Boumpas ,&nbsp;Georg Schett ,&nbsp;George Bertsias ,&nbsp;Panagiotis Garantziotis","doi":"10.1016/j.jaut.2026.103525","DOIUrl":"10.1016/j.jaut.2026.103525","url":null,"abstract":"<div><div>Insufficient treatment response is common in systemic lupus erythematosus (SLE) and may be associated with progressive organ damage, yet the molecular underpinnings of treatment resistance remain elusive. RNA sequencing was performed in blood samples from 21 SLE patients who failed to achieve Lupus Low Disease Activity State after six months of treatment with cyclophosphamide (n = 9), rituximab (n = 5), or belimumab (n = 7). Molecular endotypes were identified via unsupervised clustering of Functional Analysis of Individual Microarray Expression (FAIME) scores and cluster stability was validated in an independent cohort (n = 23). Endotype-specific druggability was assessed using the L1000CDS² platform. The pathway-based molecular stratification revealed three major endotypes among patients with inadequate treatment response: (i) a T cell-centric cluster characterized by enrichment of PD-1 signaling and DNA damage response pathways along with downregulation of CD28 co-stimulatory signaling, indicative of T cell senescence; (ii) a cytokine-driven cluster defined by elevated IL-6 and IL-17 signaling and reduced IL-2 signaling, suggesting a Th17/Treg imbalance and potential responsiveness to cytokine inhibition or low-dose IL-2 therapy; and (iii) an inflammasome-dominant cluster. A multinomial LASSO regression-derived Molecular Endotype Classification Index (MECI) - validated via 1000-fold bootstrap resampling - demonstrated potential as a surrogate marker for endotype assignment (median AUC-ROC 0.889). Transcriptome reversal analysis suggested that patients of the T cell-dominant endotype may be more responsive to CD19 CAR-T cell therapy. In summary, distinct molecular endotypes underlie insufficient response to therapy in SLE, providing a framework for personalized treatment strategies and improved clinical trial design.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103525"},"PeriodicalIF":7.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025553","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":"Immunopathogenic role of the HLA-B∗51:01-specific immunopeptidome in Behçet's disease","authors":"Yeji Lee ,&nbsp;Kyung-Cho Cho ,&nbsp;Byung Kyu Cho ,&nbsp;So Hyun Kim ,&nbsp;Jun Won Park ,&nbsp;Dongjin Shin ,&nbsp;Jong-Il Kim ,&nbsp;Insoo Kang ,&nbsp;Eugene C. Yi ,&nbsp;Eun Bong Lee","doi":"10.1016/j.jaut.2026.103523","DOIUrl":"10.1016/j.jaut.2026.103523","url":null,"abstract":"<div><h3>Objective</h3><div>The immunopeptidome, the collection of peptides bound to human leukocyte antigens (HLAs), plays a key role in initiating immune responses. HLA-B∗51:01 is an allele associated with Behçet's disease (BD). However, the role of the immunopeptidome bound to HLA-B∗51:01 in the pathogenesis of BD remains unclear.</div></div><div><h3>Methods</h3><div>We profiled the HLA-bound immunopeptidome using plasma samples from HLA-B∗51:01-positive BD and healthy controls (HCs). HLA-class I molecules were immunoprecipitated, and liquid chromatography–tandem mass spectrometry was performed to compare HLA-bound peptides between HLA-B∗51:01-positive BD with HCs. Potential HLA-B∗51:01-bound peptides, T cell epitopes, were then selected by the binding prediction software NetMHCpan. The immunogenicity of the selected peptides was investigated through enzyme-linked immunospot, flow cytometry, and dextramer staining.</div></div><div><h3>Results</h3><div>We analyzed the immunopeptidome established from BD using two different methods. First, BD-specific peptides were identified. Among 8008 peptides, 2306 were found only in BD patients. The BD-specific immunopeptidome preferred hydrophobic amino acids at position 2. Exome sequencing confirmed the presence of the identified representative peptides. These peptides, when presented on monocyte-derived dendritic cells from HLA-B∗51:01-positive BD patients, effectively activated T cells, causing them to secrete proinflammatory cytokines and express the degranulation marker CD107a. Additionally, BD-predominant peptides were identified, whose amount was increased in BD than in HC. BD-predominant peptides also activated T cells, leading to the secretion of proinflammatory cytokines.</div></div><div><h3>Conclusion</h3><div>The immunopeptidome presented on HLA-B∗51:01-positive BD is distinct from that of HLA-B∗51:01-positive HCs and can activate T cells and secrete proinflammatory cytokines; this may contribute to the pathogenesis of BD.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"159 ","pages":"Article 103523"},"PeriodicalIF":7.0,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145996489","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":"2026-01-14","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":"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":"2026-01-09","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":"Deciphering Sjögren's disease: New insights and perspectives extend from advanced omics approaches and immunology","authors":"Hu Chen ,&nbsp;Naoki Kaneko ,&nbsp;Yukiko Ohyama ,&nbsp;Masafumi Moriyama","doi":"10.1016/j.jaut.2025.103521","DOIUrl":"10.1016/j.jaut.2025.103521","url":null,"abstract":"<div><div>Sjögren's disease (SjD), formerly termed Sjögren's syndrome, is a chronic autoimmune exocrinopathy that has seen substantial advances in basic research over the past decade. Classical experimental approaches have revealed immune dysregulation encompassing aberrant activation of the adaptive immune system, activation of humoral autoimmunity against autoantigens, and upstream participation of innate immune mechanisms. In parallel, with the rapid development of sequencing and omics technologies, researchers are able to use these high-throughput methods to gain a more unbiased, sytem-wide view of disease processes and pathegenesis in SjD. Among them, numerous disease-associated traits have been revealed by genomics and epigenomics, while transcriptomics, proteomics, and immunogenomics have also depicted a more detailed landscape of phenotypes and cell states of immune cells, as well as the roles of key molecules such as Toll-like receptors (TLRs) in promoting autoimmune responses, yielding profound insights for the understanding of SjD. Meanwhile, these diverse data analysis methods offer the researchers impotant tools to further invertigate and understand SjD in the future. The convergence of these modalities supports data-driven disease prediction, refined patient stratification, and identification of therapeutic targets, thereby expanding translational opportunities. Collectively, integrating innovative omics with classical methodologies provides a coherent framework for capturing the pathogenesis of SjD, linking system-wide views to experimental validation, and accelerating the path from pathobiology to precision therapeutics. This review summarizes recent advances in the understanding of the pathogenesis of SjD, lymphomagenesis in SjD, patient stratification and promising targeted therapy, and also outlines future perspectives and challenges to be addressed.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103521"},"PeriodicalIF":7.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917686","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":"Daratumumab monotherapy reverses the immune and pro-fibrotic profiles in refractory lupus nephritis patients: a pilot case study","authors":"Dario Roccatello ,&nbsp;Alice Barinotti ,&nbsp;Massimo Radin ,&nbsp;Irene Cecchi ,&nbsp;Elena Rubini ,&nbsp;Daniele Mancardi ,&nbsp;Martina Cozzi ,&nbsp;Roberta Fenoglio ,&nbsp;Savino Sciascia","doi":"10.1016/j.jaut.2025.103520","DOIUrl":"10.1016/j.jaut.2025.103520","url":null,"abstract":"<div><div>Refractory lupus nephritis (LN) poses a significant clinical challenge in the management of systemic lupus erythematosus (SLE) due to its resistance to conventional immunosuppressive therapies. This study evaluates the immunological, anti-inflammatory and anti-fibrotic effects of daratumumab, a CD38-targeting monoclonal antibody, in patients with refractory LN who failed standard treatments. Previous findings demonstrated daratumumab safety and efficacy, improving renal function and reducing proteinuria, anti-dsDNA antibodies, and SLEDAI-2K. In the present study, daratumumab treatment resulted in immunophenotypic remodelling, including increased CD3⁺ and CD8⁺ T-cell counts and decreased B-cell populations alongside significant reductions in fibrotic and inflammatory markers (APRIL, TNF-R1, TNF-R2, TWEAK, MMP-1, MMP-2, MMP-3). Additionally, a case study of a patient with antiphospholipid antibodies (aPL) and a history of recurrent thromboses and renal flares, demonstrated an improvement in thrombin generation and endothelial function. These results suggest daratumumab to be a promising and targeted therapeutic option for managing refractory LN by modulating immune and fibrotic responses.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103520"},"PeriodicalIF":7.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880513","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":"Pathophysiological effects of long COVID-19 (auto)antibodies on fertility","authors":"Laura Talamini ,&nbsp;Cindy Verdot ,&nbsp;Yehuda Shoenfeld ,&nbsp;Sylviane Muller","doi":"10.1016/j.jaut.2025.103518","DOIUrl":"10.1016/j.jaut.2025.103518","url":null,"abstract":"<div><div>Molecular mimicry between foreign and self-antigens has long been recognized to initiate/exacerbate autoimmunity. Shared amino acid sequences have been found between SARS-CoV-2 Spike glycoprotein and human self-proteins, raising concerns about potential damages. We previously identified sequences with ≥5 identical residues shared by the SARS-CoV-2 Spike and spermatogenesis-associated proteins. One of these peptides was especially recognized by antibodies from infected, but not vaccinated individuals. Here, their pathogenic effects were explored <em>in vivo</em>. Injection of peptide antibodies into healthy male mice impaired fertility or delayed delivery time in fertile females, suggesting that cross-reactivity <em>via</em> molecular mimicry might affect the human reproductive system.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103518"},"PeriodicalIF":7.0,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833747","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}