Journal of autoimmunity最新文献

{"title":"Immunobiology of bile and cholangiocytes","authors":"Yang Li ,&nbsp;Patrick SC. Leung ,&nbsp;Weici Zhang ,&nbsp;Shucheng Zhang ,&nbsp;Zhenning Liu ,&nbsp;Mark Kurth ,&nbsp;Andrew D. Patterson ,&nbsp;M. Eric Gershwin ,&nbsp;Junmin Song","doi":"10.1016/j.jaut.2025.103376","DOIUrl":"10.1016/j.jaut.2025.103376","url":null,"abstract":"<div><div>The biliary tract is now recognized as an immune organ, and within the biliary tract, both bile and cholangiocytes play a key role in maintaining immune defense and homeostasis. First, immunoreactive proteins such as secretory IgA provide local antimicrobial effects. Second, bile acids (BAs) protect the biliary tree from immune-related injury through receptor signaling, mainly via the membrane-bound receptor TGR5 on cholangiocytes. Third, the biliary microbiota, similar to the intestinal microbiota, contributes to sustaining a stable physiobiological microenvironment. Fourth, cholangiocytes actively modulate the expression/release of adhesion molecules and cytokines/chemokines and are involved in antigen presentation; additionally, cholangiocyte senescence and apoptosis also influence immune responses. Conversely, aberrant bile composition, altered BA profiles, imbalances in the biliary microbiota, and cholangiocyte dysfunction are associated with immune-mediated cholangiopathies, including primary biliary cholangitis, primary sclerosing cholangitis, and biliary atresia. While current therapeutic agents that modulate BA homeostasis and receptor signaling have shown promise in preclinical and clinical studies, future research on biliary/intestinal microbiota and cholangiocyte function should focus on developing novel therapeutic strategies for treating cholangiopathies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103376"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074688","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":"CAR-T cell targeting three receptors on autoreactive B cells for systemic lupus erythematosus therapy","authors":"Vinayak Uppin ,&nbsp;Hunter Gibbons ,&nbsp;Marissa Troje ,&nbsp;Daniel Feinberg ,&nbsp;Beau R. Webber ,&nbsp;Branden S. Moriarity ,&nbsp;Reshmi Parameswaran","doi":"10.1016/j.jaut.2025.103369","DOIUrl":"10.1016/j.jaut.2025.103369","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated B cell activation, autoantibody production, and nephritis. B cell activating factor (BAFF) overexpression enhances autoreactive B-cell survival, driving autoimmunity. BAFF specific belimumab and CD20 specific rituximab antibodies are used for SLE therapy but are not curative, highlighting the need for alternative B cell depletion therapies. Here, we use BAFF ligand based chimeric antigen receptor T (CAR-T) cells targeting BAFFr, BCMA and TACI expressed on mature B cells and plasma cells. BAFF CAR-T cells efficiently killed B cells after co-culture with peripheral blood mononuclear cells (PBMCs) from SLE patients and in a patient derived SLE xenograft humanized mouse model developed by injecting patient PBMCs into immunocompromised mice. We also generated murine CD8⁺ T cells expressing human BAFF CAR to test their therapeutic efficacy in spontaneous (MRL/lpr) and pristane induced mouse models of SLE. In both models, BAFF CAR-T cells mediated persistent elimination of mature B cells, resulting in a decrease in the production of autoantibodies (IgM, IgG, Anti-ANA, and Anti-dsDNA IgG) and proteinuria along with prolonged survival. Adoptive transfer of B cells from control MRL/lpr lupus mice to previously BAFF CAR-T treated MRL/lpr lupus mice showed continued depletion of B cells and prolonged survival. Potential advantages of BAFF CAR-T therapy include avoiding B cell aplasia as BAFF receptors are not expressed by early B cells and preventing the escape of long-lived plasma cells post BAFF CAR-T therapy as they express receptors of BAFF. These data demonstrate the potential for a cellular immunotherapy based approach to induce remission of SLE pathogenesis using BAFF-CAR-T therapy.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103369"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary and serum cytokine profiles of patients with anti-ARS and anti-MDA5 antibodies","authors":"Kazuhiro Kurasawa ,&nbsp;Satoko Arai ,&nbsp;Yumeko Taniguchi-Namiki ,&nbsp;Sara Komatsu ,&nbsp;Aya Shimizu ,&nbsp;Anna Hasegawa ,&nbsp;Tomoka Hiyama ,&nbsp;Tomoyuki Miyao ,&nbsp;Ayae Tanaka ,&nbsp;Takayoshi Owada ,&nbsp;Hirokuni Hirata ,&nbsp;Yasutsugu Fukushima ,&nbsp;Masafumi Arima ,&nbsp;Reika Maezawa ,&nbsp;Kei Ikeda","doi":"10.1016/j.jaut.2025.103374","DOIUrl":"10.1016/j.jaut.2025.103374","url":null,"abstract":"<div><div>The present study aimed to determine the pulmonary cytokine profiles of patients with anti-RNA synthetase (ARS) and anti-melanoma differentiation-associated protein 5 (MDA5) antibodies. The study included patients with ARS and MDA5 whose serum or bronchoalveolar fluid (BALF) was available. Sandwich enzyme-linked immunoassay microarray multiplex assay was used to measure 18 cytokine levels in serum and BALF. The cytokine patterns were investigated using factor and cluster analyses. Pulmonary cytokine production was examined using the BALF/Seum cytokine ratio. Forty participants were enrolled in the study: 19 with ARS and 21 with MDA5. All patients had interstitial lung disease (ILD). BALF was collected from 10 patients with ARS and 6 with MDA5. Serum type 1 IFN, IP-10, MCP-1, and TNF-α were elevated in both ARS and MDA5. IL-6, IL-10, and IL-15 were elevated in MDA5. Serum cytokine patterns differed between ARS and MDA5. In BALF, IFN-α, IP-10, MCP-1, and ferritin were increased in both ARS and MDA5. Higher levels of IFN-α, IL-6, and ferritin were observed in MDA5. One patient with severe MDA5-ILD showed higher levels of multiple cytokines, including IL-6 and IFN-α. BALF cytokine patterns were similar in ARS and MDA5 cases except the one with severe MDA5-ILD. IL-6, IP-10, IL-15, MCP-1, and ferritin were produced in the lungs in ARS and MDA5 and IFN-α in MDA5. In conclusion, IFN-α and pulmonary macrophage activation play important roles in ILD development in both ARS and MDA5-ILD. MDA5-ILD could be characterized by higher production of multiple cytokines and macrophage activation, particularly in severe cases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103374"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065977","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":"Identification of clonally expanded T-cell receptor sequences in giant cell arteritis","authors":"Anna Weber ,&nbsp;Michal Zulcinski ,&nbsp;Lubna Haroon-Rashid ,&nbsp;Beth Kuszlewicz ,&nbsp;Alice Driessen ,&nbsp;Darren Newton ,&nbsp;Ann W. Morgan ,&nbsp;María Rodríguez Martínez","doi":"10.1016/j.jaut.2025.103372","DOIUrl":"10.1016/j.jaut.2025.103372","url":null,"abstract":"<div><h3>Background</h3><div>Arterial wall inflammation in giant cell arteritis (GCA) is characterized by T-cell infiltration and granuloma formation. There have been limited studies investigating the diversity of the T-cell receptor (TCR) repertoire in GCA patients. Here we aim to identify disease-relevant TCRs.</div></div><div><h3>Methods</h3><div>We sequenced the TCRβ repertoires in peripheral blood and biopsies from 72 GCA patients and compared them to repertoires of 60 age-matched controls. Applying K-nearest neighbours classification based on tcrdist3, an established TCR similarity measure, we identified GCA-associated TCRs across multiple model hyperparameters and experimental replicates.</div></div><div><h3>Results</h3><div>We observed that species richness and Shannon diversity were significantly lower (P = 0.0003 and P = 0.004, respectively) in GCA peripheral blood TCR repertoires compared with age-matched controls. 1526 TCRs were identified that were consistently associated with GCA, 63 TCRs were also detected in TAB repertoires. Identical GCA-associated TCRs were observed in paired blood and tissue samples from 21/30 GCA cases. 57 % of GCA-associated TCRs were fitted into 10 clusters, which displayed distinct TCR sequences and TCR V and J segment usage. TRBV20-1∗01, TRBV4-3∗01, TRBV4-2∗01 and TRBV4-1∗01 segments were over-represented and occurred at least 10 % more often among GCA patients than age-matched controls. Only 27/1526 TCR sequences had matches reported in public databases, reducing the likelihood that these targeted common infectious agents.</div></div><div><h3>Conclusions</h3><div>Our data provide evidence of circulating T-cell clonal expansions in GCA patients. Certain TCR sequence patterns were over-represented in GCA subjects. As more TCR sequences directed at human antigens become available, further analysis may ultimately reveal whether these TCRs bind a common target antigen.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103372"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143154997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of gut microbiome on immune and metabolic homeostasis in type 1 diabetes: Clinical insights for prevention and treatment strategies","authors":"Jiaqi Li,&nbsp;Zhiguo Xie,&nbsp;Lin Yang,&nbsp;Keyu Guo,&nbsp;Zhiguang Zhou","doi":"10.1016/j.jaut.2025.103371","DOIUrl":"10.1016/j.jaut.2025.103371","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) is a complex disease triggered by a combination of genetic and environmental factors, where abnormal autoimmune responses lead to progressive damage of the pancreatic β cells and severe glucose metabolism disorder. Recent studies have increasingly highlighted the close link between gut microbiota dysbiosis and the development of T1D. This review delves into existing population studies to explore the intricate interactions between the gut microbiota and the immune and metabolic homeostasis in T1D. It summarizes how changes in the structure and function of the gut microbiota are closely associated with the onset and progression of T1D across its natural course and clinical stages. More importantly, based on evidence accumulated from clinical observations and trials, we pioneer the discussion on gut microbiota-based T1D prevention and treatment strategies, this not only enriches our understanding of the complex pathological mechanisms of T1D but also provides potential directions for developing novel prevention and treatment strategies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103371"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065978","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":"Janus kinase inhibition prevents autoimmune diabetes in LEW.1WR1 rats","authors":"Adediwura Arowosegbe,&nbsp;Zhiru Guo,&nbsp;Emma Vanderleeden,&nbsp;Alan G. Derr,&nbsp;Jennifer P. Wang","doi":"10.1016/j.jaut.2025.103358","DOIUrl":"10.1016/j.jaut.2025.103358","url":null,"abstract":"<div><div>Numerous studies highlight the essential role of type I interferon (IFN) responses in type 1 diabetes. The absence of type I IFN signaling is associated with a partial reduction of autoimmune diabetes incidence in LEW.1WR1 rats. We sought to delineate type I IFN-independent mechanisms that drive diabetes using type I IFN α/β receptor (IFNAR) knockout rats. Rats were treated with polyinosinic:polycytidylic acid plus Kilham rat virus to induce diabetes. Single-cell RNA-sequencing of islets and cytokine measurements in blood and spleen from prediabetic <em>Ifnar1</em>^−/− rats were employed to identify factors driving insulitis in the global absence of IFNAR signaling. Islet immune cells were enriched for <em>Ccl4, Ccl5,</em> and <em>Ifng</em>. In addition, interleukin-1 (IL-1) was increased in spleen, and IFN-γ was increased in serum from prediabetic <em>Ifnar1</em>^−/− rats. Based on these findings, rats were treated with a C-C chemokine receptor type 5 inhibitor, an IL-1 receptor antagonist, or a nucleotide-binding oligomerization domain-like receptor family pyrin-domain containing 3 inhibitor, none of which prevented diabetes. The Janus kinase inhibitor ruxolitinib, which blocks both type I and II interferon-driven signaling, completely prevented diabetes, but only when given for a sustained period starting from the time of induction. The tyrosine kinase 2 inhibitor deucravacitinib also prevented diabetes to a significant degree. We conclude that type I and II IFNs act in concert as the main drivers of autoimmune diabetes and that inhibition of downstream signaling events for both is required for disease prevention.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103358"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006102","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":"Associations between domestic hard water exposure and incident psoriasis in adults: Insights from the UK Biobank cohort study","authors":"Rui Mao ,&nbsp;Tongtong Zhang ,&nbsp;Yun Zhong ,&nbsp;Xin Meng ,&nbsp;Caitan Yi ,&nbsp;Fan Wang ,&nbsp;Ji Li","doi":"10.1016/j.jaut.2025.103373","DOIUrl":"10.1016/j.jaut.2025.103373","url":null,"abstract":"<div><div>Although exposure to hard water is associated with various inflammatory skin conditions, the specific relationship between hard water and psoriasis has not been clearly defined. We analyzed data from 486,414 participants in the UK Biobank cohort to explore the association between domestic hard water exposure and the incidence of psoriasis. Domestic water hardness, measured in calcium carbonate concentration, was obtained in 2005 from local water providers in Wales, Scotland, and England. During a median follow-up period of approximately 14 years, a total of 4801 (1.0 %) participants reported psoriasis, and we observed that for every 50 mg/L increase in water hardness (as CaCO₃), there was a 3 % increase in the risk of psoriasis [Hazard Ratio (HR) = 1.03, 95 % Confidence Interval (CI) 1.01–1.06]. Individuals exposed to very hard water (&gt;180 mg/L) exhibited a 20 % increased risk of psoriasis compared to those exposed to soft water (0–60 mg/L) [HR: 1.20, 95 % CI: 1.07–1.34]. A positive linear relationship was observed between water hardness and the risk of psoriasis. Furthermore, the polygenic risk score indicated a synergistic effect between hard water exposure and genetic risk factors in developing psoriasis. Subgroup analysis suggested that the effect of hard water on psoriasis is more pronounced in individuals with a low polygenic risk score, women, the elderly, non-obese individuals, those of high socioeconomic status or without dyslipidemia. Residential water hardness has been identified as a significant risk factor for psoriasis in adults. Sustained efforts to reduce exposure to hard water may alleviate the psoriasis burden.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103373"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038901","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":"Diversity and function of regulatory T cells in health and autoimmune diseases","authors":"Yi Lu,&nbsp;Xiao-Yong Man","doi":"10.1016/j.jaut.2025.103357","DOIUrl":"10.1016/j.jaut.2025.103357","url":null,"abstract":"<div><div>Regulatory T cell (Treg) play a pivotal role in immune regulation and maintaining host immune homeostasis. Treg heterogeneity, characterized by diverse gene expression profiles and functional states, is complex in both health and disease. Research reveals that Tregs are not a uniform population but exhibit diversity based on their origin, location, and functional status. This heterogeneity is crucial for understanding Treg roles in various pathological conditions. Dysfunctional Tregs are closely linked to the pathogenesis of autoimmune diseases, although the precise mechanisms remain unclear. The phenotypic and functional heterogeneity of Tregs is particularly significant in diseases such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, psoriasis and autoimmune liver diseases. This review explores Treg origins, classifications, and heterogeneity in these conditions, aiming to provide new perspectives and strategies for diagnosis and treatment. Understanding Treg heterogeneity and plasticity promises to reveal novel therapeutic targets and advance precision immunotherapy development.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103357"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978548","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":"Histological pattern of non-infectious thoracic aortitis impacts mortality","authors":"Olivier Espitia ,&nbsp;Patrick Bruneval ,&nbsp;Eric Liozon ,&nbsp;Jacques Pouchot ,&nbsp;Hubert de Boysson ,&nbsp;Julien Gaudric ,&nbsp;Laurent Chiche ,&nbsp;Paul Achouh ,&nbsp;Jean-Christian Roussel ,&nbsp;Sébastien Miranda ,&nbsp;Tristan Mirault ,&nbsp;Alban Redheuil ,&nbsp;Jean-Michel Serfaty ,&nbsp;Antoine Bénichou ,&nbsp;Christian Agard ,&nbsp;Alexis F. Guédon ,&nbsp;Patrice Cacoub ,&nbsp;François Paraf ,&nbsp;Pierre-Jean Fouret ,&nbsp;Claire Toquet ,&nbsp;David Saadoun","doi":"10.1016/j.jaut.2025.103360","DOIUrl":"10.1016/j.jaut.2025.103360","url":null,"abstract":"<div><h3>Background</h3><div>Non-infectious aortitis encompasses various histological patterns, but their specific cardiovascular outcomes remain unclear.</div></div><div><h3>Objective</h3><div>To evaluate the mortality associated with non-infectious surgical thoracic aortitis.</div></div><div><h3>Methods</h3><div>This retrospective multicenter study included patients who underwent thoracic aortic surgery and had histological evidence of aortitis. The study analyzed the characteristics of patients with non-infectious aortitis presenting either a granulomatous/giant cell histological pattern or a lymphoplasmacytic pattern. Factors associated with mortality were identified using multivariate analysis.</div></div><div><h3>Results</h3><div>Among 5666 patients who underwent thoracic aortic surgery, 197 were found to have non-infectious aortitis with either a granulomatous/giant cell histological pattern (n = 138) or a lymphoplasmacytic pattern (n = 59). The overall standardized mortality rate (SMR) for patients with non-infectious surgical thoracic aortitis was 1.61 (95 % CI: 1.05; 2.39), with 31.5 % of patients dying within 10 years of the initial procedure. After a median follow-up of 3.5 years [IQR: 0.5–6.8] post-surgery, 31 % of deaths were due to aortic dissection or rupture. The 10-year cumulative incidence of death was 40.1 % (95 % CI, 17.7–61.8) for patients with a granulomatous/giant cell pattern and 14.4 % (95 % CI, 2.6–35.6) for those with a lymphoplasmacytic pattern. Granulomatous/giant cell histological pattern (HR 4.71 [vs lymphoplasmacytic pattern]; 95 % CI, 1.37–16.2; p = 0.023) and aortic dissection at diagnosis (HR 6.07 [vs aneurysm]; 95 % CI, 2.89–12.7; p &lt; 0.0001) were independently associated with increased mortality.</div></div><div><h3>Conclusion</h3><div>This multicenter study found that 31.5 % of patients with non-infectious surgical thoracic aortitis are expected to die within 10 years of their initial surgery. The granulomatous/giant cell histological pattern is associated with higher mortality.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103360"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-retinal immune response in sarcoid uveitis: A potential role for PCLO as an antigenic target","authors":"Benjamin Schrijver ,&nbsp;P. Martijn Kolijn ,&nbsp;Saad H. Hasib ,&nbsp;Josianne C.E.M. ten Berge ,&nbsp;Ikhwanuliman Putera ,&nbsp;Nicole M.A. Nagtzaam ,&nbsp;J. Conny P.A. van Holten Neelen ,&nbsp;Anton W. Langerak ,&nbsp;Marco W.J. Schreurs ,&nbsp;P. Martin van Hagen ,&nbsp;Willem A. Dik","doi":"10.1016/j.jaut.2025.103375","DOIUrl":"10.1016/j.jaut.2025.103375","url":null,"abstract":"<div><h3>Purpose</h3><div>To explore the autoimmune component of sarcoid uveitis (SU) by analyzing serum anti-retinal antibodies (ARAs), identifying targeted retinal proteins, T- and B-cell receptor repertoires and HLA genotype.</div></div><div><h3>Methods</h3><div>Material from 45 sarcoidosis patients with no presenting uveitis (SNPU) and 46 with SU was analyzed. Serum ARAs and targeted retinal layers were assessed using indirect immunofluorescence staining. HuScan analysis identified autoantibody-targeted linear epitopes. Validation included a bead-based assay for anti-Piccolo Presynaptic Cytomatrix Protein (PCLO) antibodies and an ELISpot assay for PCLO-reactive T-lymphocytes. T cell receptor beta (TCRB) and B cell receptor heavy (BCRH) repertoire analyses were performed using next-generation sequencing and HLA class II genotypes were determined by sequence-specific primer analysis.</div></div><div><h3>Results</h3><div>ARAs were more prevalent in SU patients than in SNPU patients (52 vs. 22 %, p = 0.003), with significant more reactivity against the nuclear retinal layer (32 vs. 7 %, p = 0.005). HuScan identified autoantibodies against three retinal proteins, including PCLO. Bead-based analysis showed higher anti-PCLO autoantibody levels in ARA-positive patients (median: 913.3 vs. 544.5, p = 0.035), and PCLO-directed T-lymphocytes were present in ARA-positive SU patients. Two TCRB clusters were identified in four unique ARA positive patients, while absent in ARA negative patients. No HLA allele association with ARA status could be detected.</div></div><div><h3>Conclusion</h3><div>Our findings reveal an association between serum ARA-positivity and SU, suggesting a link to autoimmune processes. An humoral and cellular response against the retinal protein PCLO was identified, highlighting PCLO as a potential autoimmune target in ARA-positive patients. Additionally, specific TCRB clusters were found to correlate with ARA status.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103375"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}