Journal of Translational Autoimmunity最新文献

{"title":"The changes in global burden of autoimmune diseases two years after the COVID-19 pandemic: a trend analysis based on the Global Burden of Disease Study 2021","authors":"Danting Zhang ,&nbsp;Wanyu Hua ,&nbsp;Fangfang Sun ,&nbsp;Chao Wen ,&nbsp;Lai Yee Cheong ,&nbsp;Ruiyan Xie ,&nbsp;Koon Ho Chan ,&nbsp;Shirley C.W. Chan ,&nbsp;Xue Li ,&nbsp;Shuang Ye ,&nbsp;Desmond Y.H. Yap","doi":"10.1016/j.jtauto.2025.100289","DOIUrl":"10.1016/j.jtauto.2025.100289","url":null,"abstract":"<div><h3>Background</h3><div>Data on the epidemiological changes in the global burden of autoimmune diseases (ADs) after the Coronavirus disease 2019 (COVID-19) pandemic is lacking. This study investigated the impact of the COVID-19 pandemic on the global burden of ADs, including psoriasis (PsO), inflammatory bowel disease (IBD), type 1 diabetes (T1DM), rheumatoid arthritis (RA), and multiple sclerosis (MS).</div></div><div><h3>Methods</h3><div>Age-standardized rates (ASR), including incidence (ASIR), prevalence (ASPR), disability-adjusted life years (DALYs), and death (ASDR), were extracted from the Global Burden of Disease Study 2021 from 1990 to 2021. The changes in number and ASR of ADs burden were assessed by absolute and relative increases comparing 2021 to 2019. Joinpoint regression analysis was used to determine whether the year 2019 marked the substantial changes in trends of ASR across global, 21 geographical regions, and 204 countries. The correlations between COVID-19 incidence, vaccination and the relative increased ASIR/ASPR of ADs were also evaluated.</div></div><div><h3>Results</h3><div>Joinpoint regression analysis identified 2019 as a pivotal year, marking a global increase in the burden of PsO. The global ASR of PsO in 2021 showed an increased incidence, prevalence, and DALYs of 0.78, 5, and 0.33 DALYs per 100,000, respectively, compared to 2019 (194.1 × 10³ cases, 1651.3 × 10³ cases, and 131.4 × 10³ DALYs, respectively). Notable absolute increases in PsO incidence rates in 2021 were observed in regions with a high socio-demographic index, particularly among individuals aged 50 to 54 and among males. Furthermore, 2019 marked a joinpoint with increased ASIR or ASPR of ADs in various regions, notably PsO in High-income North America, Southern Latin America, and South Asia, as well as IBD in Southern and Eastern Sub-Saharan Africa, Central Europe, and East Asia. Regional data from the USA, England, and Japan indicated a positive correlation between COVID-19 incidence and relative increases in the burden of PsO in 2020 (Spearman R 0.35, 0.24, and 0.36, respectively, for incidence; R 0.35, 0.2, and 0.36, respectively, for prevalence; all p &lt; 0.05). Additionally, 2021 state-level vaccination rates in the USA were negatively correlated with the relative increases in the ASIR of PsO and RA (R: 0.27 and −0.54, respectively; p &lt; 0.001 for all), as well as the ASPR of PsO, RA, and MS (R: 0.45, −0.49, and −0.41, respectively; p &lt; 0.01 for all) in 2021.</div></div><div><h3>Conclusions</h3><div>The year 2019 marked a pivotal point for increased global burden of PsO and regional burdens of other ADs. These observations have important implications for subsequent healthcare planning and resource allocation.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100289"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring the follow-up of autoimmune chronic atrophic gastritis using parietal cell antibodies and markers of gastric function","authors":"Maria Piera Panozzo ,&nbsp;Antonio Antico ,&nbsp;Nicola Bizzaro","doi":"10.1016/j.jtauto.2025.100273","DOIUrl":"10.1016/j.jtauto.2025.100273","url":null,"abstract":"<div><div>Increased interest in the pathogenesis and the evolution of autoimmune chronic atrophic gastritis (A-CAG) has led to the search for serological markers that can be used to detect changes in the gastric mucosa at an early stage and to monitor the course of the disease. Parietal cell autoantibodies have been proposed as suitable immunological markers of atrophic damage, as they can be detected in the serum when symptoms of gastritis are not yet present. However, the utility of measuring only the level of parietal cell autoantibodies in the follow-up of A-CAG does not appear to suffice. Recent evidence has suggested that, in monitoring A-CAG, parietal cell antibodies should be associated with an evaluation of gastric function through biochemical and hormonal tests, such as pepsinogens and gastrin 17. This integrated approach will allow for the more effective real-time monitoring of the state of the gastric mucosa. As A-CAG is a progressive disorder associated with an increased risk of gastric cancer and neuroendocrine tumors, the precise follow-up of patients with gastric atrophy needs to be better defined. Further longitudinal studies in large cohorts must be performed with long-term follow-up.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100273"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-tissue transcriptome-wide association study reveals novel psoriasis susceptibility genes","authors":"Fei Yan ,&nbsp;Jing Tao ,&nbsp;Jie Liu ,&nbsp;Yongliang Chen ,&nbsp;Zongju Huang","doi":"10.1016/j.jtauto.2025.100286","DOIUrl":"10.1016/j.jtauto.2025.100286","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis is a chronic, immune-mediated inflammatory skin disorder with a strong genetic component. Although numerous GWAS have identified risk loci, many associated variants lie in non-coding regions, complicating functional interpretation.</div></div><div><h3>Objective</h3><div>This study aimed to identify novel psoriasis susceptibility genes by integrating large-scale GWAS and eQTL data using a cross-tissue TWAS approach.</div></div><div><h3>Methods</h3><div>We integrated psoriasis GWAS summary statistics from the FinnGen database with GTEx V8 eQTL data. A cross-tissue TWAS was performed using UTMOST, followed by validation with single-tissue TWAS via FUSION. Conditional and joint analyses were conducted to delineate independent genetic signals, and gene-based analysis was performed using MAGMA. Causal relationships were evaluated using Mendelian randomization (MR) and Bayesian colocalization analyses. Key SNPs were functionally characterized using CADD, GERP++, and RegulomeDB for pathogenicity prediction and regulatory potential assessment. Finally, functional network analysis was conducted using GeneMANIA.</div></div><div><h3>Results</h3><div>The cross-tissue TWAS identified 259 genes significantly associated with psoriasis (p &lt; 0.05), with 12 remaining significant after FDR correction. Single-tissue TWAS validation revealed 655 significant genes, with an overlap of three protein-coding candidates: POLI, NFKB1, and ZFYVE28. Cross-validation with MAGMA refined the candidate set to NFKB1 and ZFYVE28. MR and colocalization analyses supported a causal relationship for NFKB1 in Skeletal Muscle, Transverse Colon, and Cultured Fibroblasts, and for ZFYVE28 in Subcutaneous Adipose Tissue and Esophageal Mucosa tissues. Functional annotation identified key SNPs including rs4235405, rs3774960, and rs1598856 for NFKB1, and rs1203786 for ZFYVE28, with varying degrees of pathogenicity and regulatory potential. GeneMANIA network analysis further implicated NFKB1 in NF-κB signaling and ZFYVE28 in vesicle-mediated transport.</div></div><div><h3>Conclusion</h3><div>Our integrative multi-omics approach identifies NFKB1 and ZFYVE28 as novel psoriasis susceptibility genes, providing potential biomarkers and therapeutic targets for this complex disease.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100286"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric autoimmune diseases in the light of COVID-19 pandemic, A retrospective observational big data study","authors":"Rim Kasem Ali Sliman ,&nbsp;Hilla Cohen ,&nbsp;Shereen Shehadeh ,&nbsp;Reut Batcir ,&nbsp;Yigal Elenberg Alter ,&nbsp;Keren Cohen ,&nbsp;Ilana Koren ,&nbsp;Inbal Halabi ,&nbsp;Hussein Sliman ,&nbsp;Mohamad Hamad Saied","doi":"10.1016/j.jtauto.2025.100281","DOIUrl":"10.1016/j.jtauto.2025.100281","url":null,"abstract":"<div><h3>Background</h3><div>The COVID-19 pandemic has raised concerns about potential links between SARS-CoV-2 infection and autoimmune diseases. This study investigated changes in the incidence rate (IR) of autoimmune diseases among children following the pandemic's onset.</div></div><div><h3>Methods</h3><div>A retrospective cross-sectional study analyzed data from Clalit Health Services, Israel's largest healthcare provider, examining the IR of different autoimmune diseases in children aged 0–18. The study compared pre-pandemic (2019) with pandemic/post-pandemic periods (2020–2023), encompassing a cohort of over 1.5 million children.</div></div><div><h3>Results</h3><div>Significant IR increases were observed across multiple autoimmune diseases. Rheumatic diseases (Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Henoch Schoenlein Purpura (HSP)) showed consistent increases, with HSP demonstrating the most pronounced trend. Endocrine disorders exhibited diverse patterns, with autoimmune thyroid diseases and Type 1 diabetes showing overall increases, while diabetic ketoacidosis exhibited an initial spike followed by a decline. Gastrointestinal diseases displayed heterogeneous patterns; Celiac disease and Ulcerative colitis showed general increases, Crohn's disease showed a downward trend, and autoimmune hepatitis exhibited an initial significant decrease followed by a significant increase. Dermatological conditions, including Psoriasis and Vitiligo, demonstrated consistent elevations throughout 2020–2023. Immune Thrombocytopenia Purpura showed initial decreases followed by significant increases in 2022–2023.</div></div><div><h3>Conclusions</h3><div>This comprehensive analysis reveals significant changes in pediatric autoimmune disease incidence following the COVID-19 pandemic, suggesting potential associations between SARS-CoV-2 infection and autoimmune dysregulation. The diverse patterns observed across different conditions highlight the complex interplay between viral infection and autoimmunity, emphasizing the need for continued surveillance and investigation of long-term immunological consequences of COVID-19 in pediatric populations.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100281"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases","authors":"Michaela Fehringer,&nbsp;Thomas Vogl","doi":"10.1016/j.jtauto.2025.100269","DOIUrl":"10.1016/j.jtauto.2025.100269","url":null,"abstract":"<div><div>Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes). This similarity can lead to cross-reactive antibodies and T-cell receptors, resulting in an immune response against autoantigens. Both commensal microbes in the human microbiome and pathogens can trigger molecular mimicry, thereby potentially contributing to the onset of ARDs.</div><div>In this review, we focus on the role of molecular mimicry in the onset of rheumatoid arthritis and systemic lupus erythematosus. Moreover, implications of molecular mimicry are also briefly discussed for ankylosing spondylitis, systemic sclerosis and myositis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100269"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune characterization of lupus nephritis patients undergoing dialysis","authors":"Quentin Simon ,&nbsp;François Gaillard ,&nbsp;John Tchen ,&nbsp;Delphine Bachelet ,&nbsp;Karim Sacré ,&nbsp;Katell Peoc'h ,&nbsp;Noémie Jourde-Chiche ,&nbsp;Eric Daugas ,&nbsp;Nicolas Charles","doi":"10.1016/j.jtauto.2025.100290","DOIUrl":"10.1016/j.jtauto.2025.100290","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) activity decreases in some patients with end-stage kidney disease (ESKD). The impact of ESKD on the immune cell profile of SLE patients and lupus activity remains unclear. In this study, we aimed at characterizing immunologically inactive and active SLE patients undergoing dialysis therapy. Based on multi-parametric flow cytometry assays, an extensive immunophenotyping was performed on blood samples from 47 SLE patients undergoing hemodialysis, 10 non-dialyzed SLE patients with active lupus nephritis (aLN), 6 non-dialyzed patients with a history of LN currently in remission (rLN), and 20 healthy volunteers (HV) as controls (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: NCT03921398). The hemodialysis group was composed of 16 SLE patients with inactive disease (iHD), 22 with sustained low disease activity with a non-renal SLEDAI ≤4 (aHD≤4), and 9 highly active SLE patients (aHD&gt;4). A factorial discriminant analysis was performed to validate the association between immune cell signatures and lupus activity. By compiling 12 cellular variables, we describe immune profiles related to highly active SLE patients or associated with both inactive and low-disease activity groups. As non-dialyzed active SLE patients, active patients undergoing hemodialysis showed a specific combination of increased numbers of circulating CD19^hi CD27^– “atypical naive” B cells, plasmablasts, CD16⁺ inflammatory monocytes and a basopenia. This study brings a comprehensive overview of immune cell signatures observed in SLE patients undergoing dialysis. We propose a simple immunophenotypic approach for the assessment of lupus activity that may provide help to data-driven personalized medicine in hemodialyzed SLE patients.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100290"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies as prognostic markers in rheumatoid arthritis","authors":"Carl Turesson ,&nbsp;Johan Rönnelid ,&nbsp;Alf Kastbom","doi":"10.1016/j.jtauto.2025.100291","DOIUrl":"10.1016/j.jtauto.2025.100291","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressively destructive polyarthritis. Key autoimmune features include the presence of autoantibodies. The purpose of this review is to discuss the diagnostic and prognostic properties of rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA), based on current use in Sweden. Furthermore, we discuss their relation to disease outcomes and their importance for management of patients with RA.</div></div><div><h3>Principal findings</h3><div>Based on current cut-offs, ACPA has a higher specificity for RA than RF, and testing for ACPA alone is recommended when investigating patients with clinically suspect RA. The diagnostic utility of RF may improve with adjusted reference range/upper limit of normal.</div><div>RF and ACPA both predict rapid radiographic progression, severe extra-articular manifestations and mortality, whereas other outcomes, such as osteoporosis, pain and disability are not as clearly related to seropositivity. RF/ACPA positive patients respond better to some targeted therapies, in particular rituximab, compared to seronegative RA patients. Recent studies indicate that treatment of ACPA-positive arthralgia with abatacept may delay and perhaps sometimes even prevent development of arthritis. Available evidence does not support an added value of repeated RF or ACPA testing.</div></div><div><h3>Conclusions</h3><div>Testing for ACPA in patients with arthralgia or suspected early RA, and for ACPA and RF at RA diagnosis, provides useful diagnostic and prognostic information, which has implications for follow-up and treatment. Repeated testing for ACPA and RF is not recommended. Potential future developments include treatment of ACPA-positive individuals for prevention of arthritis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100291"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus","authors":"Chen-xing Zhang ,&nbsp;You-ying Mao ,&nbsp;Yu-pin Tan ,&nbsp;Mei-yu Zhang ,&nbsp;Kang Shao ,&nbsp;Shu-jun Wang ,&nbsp;Ping Ji ,&nbsp;Jia-yuan Wang ,&nbsp;Lei Yin ,&nbsp;Ying Wang","doi":"10.1016/j.jtauto.2025.100276","DOIUrl":"10.1016/j.jtauto.2025.100276","url":null,"abstract":"<div><h3>Objective</h3><div>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-α on CD8⁺T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-α in regard to dysfunction of CD8⁺T cells in SLE.</div></div><div><h3>Methods</h3><div>Serum level of IFN-α was detected in SLE and healthy controls (HC). Surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a) and secretion of granzyme B of CD8⁺T cells was measured in SLE and HC with or without IFN-α co-stimulation/PI3K inhibitor.</div></div><div><h3>Results</h3><div>Our results demonstrated that there was increased surface expression of CD107a of CD8⁺T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8⁺T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8⁺T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-α in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8⁺T cells was upregulated upon IFN-α costimulation, which was consistent with enhanced cytotoxicity of CD8⁺T cells upon IFN-α costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-α costimulation in a dose-dependent manner.</div></div><div><h3>Conclusion</h3><div>In summary, elevated serum level of IFN-α was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8⁺T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100276"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice","authors":"Liqi Zhu ,&nbsp;Yuanyuan Liang ,&nbsp;Linghan Yang ,&nbsp;Qihui Yang ,&nbsp;Jun Yin ,&nbsp;Tao Wang ,&nbsp;Xiangming Xu ,&nbsp;Quan Zhang","doi":"10.1016/j.jtauto.2025.100275","DOIUrl":"10.1016/j.jtauto.2025.100275","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune hepatitis (AIH) is a chronic progressive liver disease caused by the immune system mistakenly attacking its own hepatocytes. The role of the gut microbiome in the pathogenesis and progression of AIH is of considerable significance. However, the dearth of suitable animal models has significantly constrained advancements in the pathogenesis and the development of therapeutic strategies for AIH. <em>Helicobacter mastomyrinus</em> (<em>H. mastomyrinus,</em> Hm) is a potentially zoonotic pathogenic microorganism capable of causing diseases of the enterohepatic system in rodent laboratory animals. Nevertheless, research on its role and mechanisms in causing liver disease is severely limited.</div></div><div><h3>Methods</h3><div>In this study, male BALB/c mice were infected with Hm isolate Hm-17, and were sacrificed at 4 w, 8 w, 14 w and 22 w after infection, respectively. The serum was collected for detecting a number of AIH indicators, including the aminotransferases level, IgG content and autoantibody level. Additionally, the liver tissue was examined for pathological analysis, fibrosis, bacterial content, and the distribution of immune cells.</div></div><div><h3>Results</h3><div>It was observed that the infection initially caused focal necrotizing hepatitis and subsequently progressed to interface hepatitis with lymphocyte/plasma cell infiltration, as well as hypergammaglobulinemia and autoantibody reactions, predominantly to Anti-nuclear and anti-smooth muscle antibodies. Furthermore, as the infection persisted, the mice exhibited a progressive increase in liver fibrosis and mild steatosis. Despite the maintenance of a low level of Hm colonization in the liver, there was a notable infiltrate of macrophages, T and B lymphocytes. In particular, the inflammatory foci in the Hm-infected liver were highly enriched for IL17⁺ cells.</div></div><div><h3>Conclusion</h3><div>The present study provides an animal model of immunological liver injury induced by Hm infection that exhibits main characteristics similar to those observed in AIH-1 patients. This model may serve as a novel animal model for the study of the pathogenesis and potential therapeutic strategies for human AIH.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100275"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The antibody repertoire of autoimmune sensory neuronopathies targets pathways of the innate and adaptive immune system. An autoantigenomic approach","authors":"Christian P. Moritz ,&nbsp;Yannick Tholance ,&nbsp;Nadia Boutahar ,&nbsp;Coralie Borowczyk ,&nbsp;Anne-Emmanuelle Berger ,&nbsp;Stéphane Paul ,&nbsp;Jean-Christophe Antoine ,&nbsp;Jean-Philippe Camdessanché","doi":"10.1016/j.jtauto.2025.100277","DOIUrl":"10.1016/j.jtauto.2025.100277","url":null,"abstract":"<div><div>Sensory neuronopathies (SNN) encompass diverse etiologies, with autoimmunity playing a major role through both cellular and humoral responses. To investigate the humoral autoantibody repertoire in autoimmune SNN, we conducted a retrospective cohort study using large Human Proteome-wide protein microarrays (HuProt 3.1, HuProt 4.0, ProtoArrays). We specifically analyzed immune system pathways targeted within the autoantigen repertoire (the autoantigenome). We included 131 participants: 44 patients with non-paraneoplastic autoimmune SNN (12 with anti-FGFR3 and/or anti-AGO antibodies), 8 with paraneoplastic SNN, and 79 controls. Findings were validated in an independent cohort of 16 SNN patients. Overrepresentation of immune-system-related proteins was assessed using the Reactome database, and serum levels of IFN-γ and IL-6 were measured with the Bio-Plex Pro™ Reagent Kit. Autoimmune SNN sera interact with significantly more immune system proteins than healthy controls (ProtoArrays: 271/863 vs. 14/863, HuProt: 112/1694 vs. 39/1694, both p &lt; 0.0001). Overrepresentation was observed across all major immune sub-pathways, including innate and adaptive immune responses as well as cytokine signaling. Anti-FGFR3-positive SNN patients showed more frequent reactivity to immune system proteins than anti-FGFR3-negative ones. The independent SNN cohort validated the overrepresentation of targeted immune system pathways. Validation with dot blot and ELISA confirmed reactivity to TRIM21 and IL-6 and identified anti-IFN-γ-positive SNN patients. IFN-γ levels correlated weakly with levels of anti-IFN-γ antibodies (Pearson's <em>r</em> = 0.22, p = 0.03). We conclude that the antibody repertoire of autoimmune SNN targets pathways of the innate and adaptive immune system, potentially reflecting key disease-related immune pathways and highlighting the systemic role of immune dysregulation in SNN.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100277"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}