Journal of autoimmunity最新文献

{"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}

{"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":"2026-02-01","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}

{"title":"Striatin-3 is a human autoantigen but it is not associated with the S-phase G2 nuclear antigen (SG2NA) staining pattern","authors":"Marvin J. Fritzler ,&nbsp;Yoshinao Muro ,&nbsp;Werner Klotz ,&nbsp;Manfred Herold ,&nbsp;Luis E.C. Andrade ,&nbsp;Marcelle Grecco ,&nbsp;Minoru Satoh ,&nbsp;May Y. Choi ,&nbsp;Maria Infantino ,&nbsp;Edward K.L. Chan","doi":"10.1016/j.jaut.2025.103503","DOIUrl":"10.1016/j.jaut.2025.103503","url":null,"abstract":"<div><div>Human autoantibodies have a long history of being valuable reagents to identify and characterize unique subcellular compartments, macromolecular complexes, and their individual components. One such discovery started as a unique cell-cycle related immunofluorescence pattern characterized as autoantibody targets localized in S and G2 phase nuclei of tissue culture cells, which became known as the “SG2NA” (SG2 nuclear antigen). These descriptions were followed by the identification of a calmodulin-binding protein family named ‘striatin’ that was later identified as three paralogs: Striatin/STRN1, Striatin-3/STRN3/SG2NA, and Striatin-4/STRN4/Zinedin. Many subsequent reports have used the designations SG2NA and striatin interchangeably. This report reviews the history of SG2NA and clarifies that striatin-3 is indeed a target autoantigen of some autoimmune sera, but commercially available striatin-3 antibodies or human sera that react with striatin-3 do not produce a SG2 phase nuclear staining pattern on HEp-2 cells. Hence, future reports should not use anti-SG2NA and anti-striatin interchangeably.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103503"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584340","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":"Physical work demands and risk of rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus. A Danish longitudinal cohort study","authors":"Helena Breth Nielsen ,&nbsp;Nidhi Gupta ,&nbsp;Astrid Juhl Andersen ,&nbsp;Lene Wohlfahrt Dreyer ,&nbsp;Esben Meulengracht Flachs ,&nbsp;Ida E.H. Madsen ,&nbsp;Henrik Albert Kolstad ,&nbsp;Hans Kromhout ,&nbsp;Camilla Sandal Sejbaek ,&nbsp;Karin Sørig Hougaard","doi":"10.1016/j.jaut.2025.103514","DOIUrl":"10.1016/j.jaut.2025.103514","url":null,"abstract":"<div><h3>Objectives</h3><div>This study assesses the association between physical work demands and rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE) among men and women.</div></div><div><h3>Methods</h3><div>This nationwide, register-based study included more than 1.0 million women and 1.1 million men with employment born between 1960 and 1999 from the Danish Occupational Cohort with eXposure data (DOC∗X). Information on physical work demands was obtained from a job exposure matrix (JEM) and measured as recent physical work demands, accumulated physical work demands, and years with high physical work demands since workforce entry. The populations were followed from 1997 to 2018. Poisson regression models were used to estimate the IRRs for developing RA, SSc, and SLE, identified in the Danish National Patient Registry.</div></div><div><h3>Results</h3><div>Men in occupations with high recent physical work demands (4th quartile vs. 1st quartile: 1.36, 95 % CI 1.31–1.42), higher accumulated physical work demands, and more years with high physical work demands, had a higher risk of diagnosis of RA, while this was not the case for women. Accumulated physical work demands and more years with high physical work demands were associated with a small increased risk of diagnosis of SSc and SLE among men. In women, high physical work demands were associated with a reduced risk of diagnosis of SLE, while the results on SSc were inconsistent.</div></div><div><h3>Conclusion</h3><div>These findings support an association between higher physical work demands and diagnosis of RA and possibly, albeit to a lesser extent, SLE and SSc in men, but not in women.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"158 ","pages":"Article 103514"},"PeriodicalIF":7.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734026","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":"2026-02-01","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}