Journal of autoimmunity最新文献

{"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}

{"title":"Primary Cesarean delivery and future risk of maternal autoimmune disease: A population-based cohort study","authors":"Natalie V. Scime ,&nbsp;Sonia M. Grandi ,&nbsp;Mary A. De Vera ,&nbsp;Cindy-Lee Dennis ,&nbsp;Alexa Boblitz ,&nbsp;Hilary K. Brown","doi":"10.1016/j.jaut.2025.103370","DOIUrl":"10.1016/j.jaut.2025.103370","url":null,"abstract":"<div><h3>Objectives</h3><div>To determine the association between primary Cesarean delivery and incident autoimmune disease in women.</div></div><div><h3>Methods</h3><div>We conducted a population-based cohort study of 253,901 females in Ontario, Canada with a first childbirth between 2012 and 2017 and with no pre-existing autoimmune disease. Royston-Parmar models were used to estimate the time-varying association between Cesarean delivery (28.2 % of females) versus vaginal delivery (71.8 % of females; referent) and celiac disease, multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic autoimmune rheumatic disease (SARD), separately, from date of delivery to date of diagnosis or censoring at death, loss of health insurance, or March 31, 2021. To account for potential confounding by indication for Cesarean delivery, models were generated using (i) overlap weighting based on propensity scores for mode of delivery and (ii) with restriction to low-risk pregnancies free of pre-labour Cesarean indications (n = 146,887).</div></div><div><h3>Results</h3><div>At up to 9 years following childbirth (median = 6.5 years of follow-up), Cesarean delivery was associated with an increased risk of MS, but not celiac disease, RA, or SARD. Overall, cumulative incidence of MS was 0.28 % following Cesarean delivery and 0.21 % following vaginal delivery. After overlap weighting, the adjusted hazard ratio (AHR) curve formed a slight L-shape with the largest magnitude between birth and 3 years (1-year AHR 1.37, 95 % CI 1.04–1.69) and diminishing thereafter (5-year 1.23, 95 % CI 0.91–1.55; 7-year 1.21, 95 % CI 0.84–1.57). Results were similar when restricted to births following low-risk pregnancies.</div></div><div><h3>Conclusions</h3><div>Findings suggest a possible link between Cesarean delivery and MS development among females that warrants future replication and explanatory studies.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"151 ","pages":"Article 103370"},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080091","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":"AIM2 deficiency in CD4+ T cells promotes psoriasis-like inflammation by regulating Th17-Treg axis via AIM2-IKZF2 pathway","authors":"Yue Xin ,&nbsp;Ming Yang ,&nbsp;Zhidan Zhao ,&nbsp;Zhenghao He ,&nbsp;Yang Mei ,&nbsp;Feng Xiong ,&nbsp;Fen Tan ,&nbsp;Anqun Chen ,&nbsp;Christopher Chang ,&nbsp;Helong Dai ,&nbsp;Haijing Wu ,&nbsp;Qianjin Lu","doi":"10.1016/j.jaut.2024.103351","DOIUrl":"10.1016/j.jaut.2024.103351","url":null,"abstract":"<div><div>Psoriasis vulgaris remains a common inflammatory skin disease globally. The imbalance between Th17 and Treg cells plays an integral role in the pathogenesis of psoriasis vulgaris, but the underlying mechanisms remain obscure. The role of AIM2 in Treg cell function in psoriasis is unclear. We found that AIM2 expression is upregulated in peripheral blood and skin lesions from patients with psoriasis vulgaris when compared with healthy controls. In a psoriasis-like mouse model, <em>CD4</em>^<em>cre</em><em>Aim2</em>^{<em>fl/fl</em>} mice showed aggravated psoriatic symptoms, increased Th17 cell and decreased Treg cell numbers in spleens and dLNs compared to <em>Aim2</em>^{<em>fl/fl</em>} mice. The loss of AIM2 in naïve CD4⁺ T cells promotes Th17 cell differentiation and decreases Treg cell numbers <em>in vitro</em>. Further, IKZF2 was identified as a downstream regulator of AIM2 through RNAseq analysis. AIM2 deficiency in CD4⁺ T cells downregulated IKZF2 mRNA expression. Silencing IKZF2 in naïve CD4⁺ T cells led to a significant increase in the expression of RORc and diminished FOXP3 expression. In summary, AIM2 may regulate the differentiation of Th17 and Treg cell by affecting IKZF2. Our findings might shed light on the pathogenesis of psoriasis and provide potential therapeutic targets for patients with psoriasis.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"150 ","pages":"Article 103351"},"PeriodicalIF":7.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846777","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":"External and internal exposome as triggers of biological signalling in systemic sclerosis – A narrative synthesis","authors":"Lisa MF. Janssen ,&nbsp;Frauke Lemaire ,&nbsp;Chiara Longo Sanchez-Calero ,&nbsp;François Huaux ,&nbsp;Steven Ronsmans ,&nbsp;Peter HM. Hoet ,&nbsp;Manosij Ghosh","doi":"10.1016/j.jaut.2024.103342","DOIUrl":"10.1016/j.jaut.2024.103342","url":null,"abstract":"<div><div>Systemic sclerosis (SSc) is an autoimmune chronic connective tissue disorder with a complex pathogenesis and a strong gene-environment interaction. Despite the low prevalence of SSc, with around 100–250 cases per million, the morbidity and mortality are high and disproportionately affecting women. In this context, we review the influence of the external and internal exposome on the “immunome” in SSc. While several studies have addressed aspects of exposure-induced autoimmunity in general, very few have focused on SSc-specific phenotypes. In epidemiological studies, targeted characterization of the external exposome component in relation to SSc has often been limited to a single exposure. Despite the selective characterization of exposure, such studies play an important role in providing evidence that can be used towards reduction of exposure of modifiable factors, and can lead to proper management and prevention of SSc. Additionally, there is an effort towards integration of external exposome data with health data (health records, medical imaging, diagnostic results, etc.), to significantly improve our understanding of the environmental and occupational causes of SSc. A limited number of studies have identified biological processes related to the vascular homeostasis, fibrotic processes and the immune system. The key findings of the current review show advances in our understanding of the SSc disease phenotype and associated biomarkers in relation to specific pathophysiological features, however most often such studies are not supplemented with external exposome data.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"150 ","pages":"Article 103342"},"PeriodicalIF":7.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791803","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":"Maternal autoimmune systemic connective tissue disease and vasculitis and electrocardiographic findings in the offspring","authors":"Sarah Sofie Andersen ,&nbsp;Terese Frellesen Neumann ,&nbsp;Sofie Dannesbo ,&nbsp;Anna Axelsson Raja ,&nbsp;Ruth Ottilia Birgitta Vøgg ,&nbsp;Heather Allison Boyd ,&nbsp;Karen Schreiber ,&nbsp;Maria Munk Pærregaard ,&nbsp;Alex Hørby Christensen ,&nbsp;Kasper Karmark Iversen ,&nbsp;Henning Bundgaard ,&nbsp;Anne-Sophie Sillesen","doi":"10.1016/j.jaut.2025.103356","DOIUrl":"10.1016/j.jaut.2025.103356","url":null,"abstract":"<div><h3>Introduction</h3><div>Maternal autoimmune systemic connective tissue diseases (CTDs) and their related antibodies have been associated with adverse fetal outcomes, including complete heart block. In this study, we assessed the association between maternal CTD or vasculitis and neonatal electrocardiographic (ECG) parameters.</div></div><div><h3>Methods</h3><div>Our study population was drawn from the Copenhagen Baby Heart Study (CBHS), a prospective, population-based cohort study open to all neonates born in the Copenhagen area. All CBHS neonates born to mothers with CTD or vasculitis were matched 1:3 to neonates born to mothers without these diseases on sex, gestational age, age and weight at time of examination, and maternal age at delivery. Maternal CTD and vasculitis diagnoses were validated through medical record review. Our primary analyses compared ECG parameters for exposed and unexposed neonates overall. Where numbers allowed, subanalyses were then conducted by specific CTD diagnoses and autoantibody types.</div></div><div><h3>Results</h3><div>Among 17,862 CBHS neonates with an available ECG, 40 neonates of mothers with CTDs or vasculitis (50 % males, median age 12 [interquartile range 8–16] days) were matched to unexposed neonates. Overall, no significant differences in heart rate, PR interval, QRS axis, QRS duration, QT/QTc interval, or R- or S-wave amplitudes were found when comparing exposed and unexposed neonates (all p &gt; 0.05). Similarly, separate analyses of the 10 neonates with anti-Ro/SSA-positive mothers and their matched comparators revealed no significant between-group differences. However, neonates born to mothers with antiphospholipid syndrome (n = 15) had a significantly longer QRS duration (median 56 ms vs. 52 ms, p = 0.02) and corrected QT interval (median QTcBaz 430 ms vs. 414 ms, p = 0.01), compared with matched unexposed neonates.</div></div><div><h3>Conclusion</h3><div>In this population-based study, no significant overall differences in ECG parameters were found between neonates exposed to maternal CTD or vasculitis and unexposed neonates. However, neonates exposed to maternal antiphospholipid syndrome had significantly longer QRS- and QTc intervals than unexposed neonates. The potential clinical implications of these findings are unknown and, combined with the limitations of this study, warrant further investigation in larger cohorts.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"150 ","pages":"Article 103356"},"PeriodicalIF":7.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142965132","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":"Effect of Epstein-Barr Virus infection on gene regulation in immune cells of patients with Immune-Mediated Diseases","authors":"Yuko Akutsu ,&nbsp;Mineto Ota ,&nbsp;Takahiro Itamiya ,&nbsp;Masaaki Mori ,&nbsp;Tomohiro Morio ,&nbsp;Kazuhiko Yamamoto ,&nbsp;Tomohisa Okamura ,&nbsp;Keishi Fujio","doi":"10.1016/j.jaut.2024.103355","DOIUrl":"10.1016/j.jaut.2024.103355","url":null,"abstract":"<div><div>It has been known that Epstein-Barr virus (EBV) can latently infect immune cells after the initial infection, and epidemiological studies have suggested its association with the onset of immune-mediated diseases (IMDs). However, the specific impact of EBV infection on IMDs pathology remains unclear. We quantified EBV load of B cell subsets (Naïve B cells, Unswitched memory B cells, Switched memory B cells, Double negative B cells, and Plasmablasts) in IMD patients as well as healthy control (HC) using bulk RNA sequencing data of 504 donors. The EBV load was clearly higher in IMD patients compared to HC. Furthermore, the wide range of EBV load in this dataset enabled us to assess the impact of EBV load on gene regulation. We found many examples of expression quantitative trait loci (eQTL) whose effects were associated with EBV load. Expression QTLs that exhibited larger effects with increasing EBV load were significantly overlapped with binding sites of transcription factors derived from the EBV genome. These EBV load-associated eQTLs exhibited high enrichment of systemic lupus erythematosus (SLE) GWAS signals, suggesting the mechanical link of EBV infection and the onset of the disease via gene regulation. These findings provide the first evidence of the influence of EBV infection on gene regulation in human primary cells and its association with the SLE onset and/or progression.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"150 ","pages":"Article 103355"},"PeriodicalIF":7.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949502","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":"Advances in chimeric antigen receptor T cell therapy for autoimmune and autoinflammatory diseases and their complications","authors":"Liuting Zeng ,&nbsp;Yan Li ,&nbsp;Wang Xiang ,&nbsp;Wei Xiao ,&nbsp;Zhiyong Long ,&nbsp;Lingyun Sun","doi":"10.1016/j.jaut.2024.103350","DOIUrl":"10.1016/j.jaut.2024.103350","url":null,"abstract":"<div><div>Chimeric antigen receptor T (CAR-T) cells are genetically engineered T cells expressing transmembrane chimeric antigen receptors with specific targeting abilities. As an emerging immunotherapy, the use of CAR-T cells has made significant breakthroughs in cancer treatment, particularly for hematological malignancies. The success of CAR-T cell therapy in blood cancers highlights its potential for other conditions in which the clearance of pathological cells is therapeutic, such as liver diseases, infectious diseases, heart failure, and diabetes. Given the limitations of current therapies for autoimmune diseases, researchers have actively explored the potential therapeutic value of CAR-T cells and their derivatives in the field of autoimmune diseases. This review focuses on the research progress and current challenges of CAR-T cells in autoimmune diseases with the aim of providing a theoretical basis for the precise treatment of autoimmune diseases. In the future, CAR-T cells may present new therapeutic modalities and ultimately provide hope for patients with autoimmune diseases.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"150 ","pages":"Article 103350"},"PeriodicalIF":7.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864279","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":"Circulating T cells in sarcoidosis have an aberrantly activated phenotype that correlates with disease outcome","authors":"Jelle R. Miedema ,&nbsp;Lieke J. de Jong ,&nbsp;Denise van Uden ,&nbsp;Ingrid M. Bergen ,&nbsp;Mirjam Kool ,&nbsp;Caroline E. Broos ,&nbsp;Vivienne Kahlmann ,&nbsp;Marlies S. Wijsenbeek ,&nbsp;Rudi W. Hendriks ,&nbsp;Odilia B.J. Corneth","doi":"10.1016/j.jaut.2023.103120","DOIUrl":"10.1016/j.jaut.2023.103120","url":null,"abstract":"<div><h3>Rationale</h3><div>Disease course in sarcoidosis is highly variable. Bronchoalveolar lavage fluid and mediastinal lymph nodes show accumulation of activated T cells with a T-helper (Th)17.1 signature, which correlates with non-resolving sarcoidosis. We hypothesize that the peripheral blood (PB) T cell phenotype may correlate with outcome.</div></div><div><h3>Objectives</h3><div>To compare frequencies, phenotypes and function of circulating T cell populations in sarcoidosis patients with healthy controls (HCs) and correlate these parameters with outcome.</div></div><div><h3>Methods</h3><div>We used multi-color flow cytometry to quantify activation marker expression on PB T cell subsets in treatment-naïve patients and HCs. The disease course was determined after 2-year follow-up. Cytokine production was measured after T cell stimulation <em>in vitro.</em></div></div><div><h3>Measurements and main results</h3><div>We observed significant differences between patients and HCs in several T cell populations, including CD8⁺ and CD4⁺ T cells, Th1/Th17 subsets, CD4⁺ T memory stem cells, regulatory T cells (Tregs) and γδ T cells. Decreased frequencies of CD4⁺ T cells and increased frequencies of Tregs and CD8⁺ γδ T cells correlated with worse outcome. Naïve CD4⁺ T cells displayed an activated phenotype with increased CD25 expression in patients with active chronic disease at 2-year follow-up. A distinctive Treg phenotype with increased expression of CD25, CTLA4, CD69, PD-1 and CD95 correlated with chronic sarcoidosis. Upon stimulation, both naïve and memory T cells displayed a different cytokine profile in sarcoidosis compared to HCs.</div></div><div><h3>Conclusions</h3><div>Circulating T cell subpopulations of sarcoidosis patients display phenotypic abnormalities that correlate with disease outcome, supporting a critical role of aberrant T cell activation in sarcoidosis pathogenesis.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103120"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677871","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":"Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities","authors":"Esther Erdei ,&nbsp;Elena R. O'Donald ,&nbsp;Li Luo ,&nbsp;Kendra Enright ,&nbsp;Marcia O'Leary ,&nbsp;Debra MacKenzie ,&nbsp;John Doyle ,&nbsp;Margaret Eggers ,&nbsp;Deborah Keil ,&nbsp;Johnnye Lewis ,&nbsp;Jeffrey A. Henderson ,&nbsp;Robert L. Rubin","doi":"10.1016/j.jaut.2023.103117","DOIUrl":"10.1016/j.jaut.2023.103117","url":null,"abstract":"<div><div>Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, <em>in vivo</em> levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.</div></div>","PeriodicalId":15245,"journal":{"name":"Journal of autoimmunity","volume":"149 ","pages":"Article 103117"},"PeriodicalIF":7.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182635","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}