Journal of Translational Autoimmunity最新文献

{"title":"The ‘autoimmunome’ of centenarians","authors":"Pedro Carrera-Bastos ,&nbsp;Abel Plaza-Florido ,&nbsp;Alejandro Santos-Lozano ,&nbsp;Vânia Borba ,&nbsp;Gabriel Rodríguez-Romo ,&nbsp;Celia García-Chico ,&nbsp;Simone Lista ,&nbsp;Gonzalo Saco-Ledo ,&nbsp;Enzo Emanuele ,&nbsp;Yehuda Shoenfeld ,&nbsp;Alejandro Lucia","doi":"10.1016/j.jtauto.2025.100295","DOIUrl":"10.1016/j.jtauto.2025.100295","url":null,"abstract":"<div><h3>Objective</h3><div>To identify signature proteins potentially linked to resistance to autoimmunity in the blood of centenarians.</div></div><div><h3>Methods</h3><div>We conducted <em>in silico</em> data mining of previously published proteomic results using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and PHENOPEDIA databases.</div></div><div><h3>Results</h3><div>Sixteen autoimmune disease-related proteins were identified within the proteomic signatures of centenarians. Albumin was the most connected hub protein, notably elevated in centenarians compared to younger controls, suggesting a protective role. Eight of the identified autoimmunity-related proteins—ADIPOQ, C1S, C5, C7, C9, CFD, MASP1, and SERPING1—were associated with the complement system.</div></div><div><h3>Conclusion</h3><div>Elevated albumin levels and a prominent complement system presence in centenarians' blood proteome may contribute to resistance to autoimmunity, highlighting potential protective mechanisms against autoimmune diseases in extreme longevity.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100295"},"PeriodicalIF":4.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255113","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":"A comparative study of different assays for autoantibodies detection in patients with autoimmune gastritis","authors":"Małgorzata Osmola ,&nbsp;Caroline Hémont ,&nbsp;Marcin Romańczyk ,&nbsp;Amaury Druet ,&nbsp;Nicolas Chapelle ,&nbsp;Tamara Matysiak-Budnik ,&nbsp;Marco Vincenzo Lenti ,&nbsp;Jérôme C. Martin","doi":"10.1016/j.jtauto.2025.100294","DOIUrl":"10.1016/j.jtauto.2025.100294","url":null,"abstract":"<div><h3>Objective</h3><div>Autoimmune gastritis (AIG) is an important health problem and a risk factor for gastric neoplasms. This study assessed the diagnostic performance of different assays for anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) in patients with histologically confirmed AIG.</div></div><div><h3>Methods</h3><div>This prospective, multicenter study included 50 AIG patients and 93 controls. The diagnostic performance of fluorescent enzyme immunoassay (FEIA) and immunoblot was evaluated for the detection of both APCA and AIFA, while indirect immunofluorescence (IIF) was assessed for APCA only.</div></div><div><h3>Results</h3><div>Overall, AIFA detection using FEIA demonstrated slightly better performance (specificity [Sp] 100 %, positive predictive value [PPV] 100 %, negative predictive value [NPV] 75 %) compared to immunoblot (Sp 98.9 %, PPV 94.1 %, NPV 73 %). However, both methods showed low sensitivity (Se): 38 % for FEIA and 32 % for immunoblot. When the FEIA cut-off was adjusted using ROC curve analysis, Se increased to 50 %, while maintaining high Sp (98.9 %). For APCA detection, Se was similar across all methods (∼80 %), but Sp varied: immunoblot showed lower Sp (89.3 %) compared to IIF (98.8 %) and FEIA (95.7 %). PPV was highest for IIF (97.5 %), followed by FEIA (89.9 %) and immunoblot (89.3 %). NPV was lowest for immunoblot (80 %), while IIF and FEIA showed comparable values (89.5 % and 90.9 %, respectively). Adjusting the FEIA cut-off for APCA increased Sp to 98.9 % without reducing Se (76 %). Combining AIFA and APCA testing improved diagnostic performance, yielding a sensitivity of 90 % and specificity of 95.7 %.</div></div><div><h3>Conclusions</h3><div>FEIA offers superior diagnostic accuracy for APCA and AIFA testing in AIG. The highest diagnostic yield for AIG is observed when both APCA and AIFA are assessed. This approach could be clinically applicable in the screening for AIG and diagnostic process of AIG.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100294"},"PeriodicalIF":4.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167145","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":"Epigenetic regulation of thrombo-inflammation in Behçet and antiphospholipid syndrome","authors":"Alessandra Bettiol ,&nbsp;Giacomo Bagni ,&nbsp;Francesca Di Patti ,&nbsp;Elena Lastraioli ,&nbsp;Alice Barinotti ,&nbsp;Massimo Radin ,&nbsp;Savino Sciascia ,&nbsp;Domenico Prisco ,&nbsp;Annarosa Arcangeli ,&nbsp;Giacomo Emmi","doi":"10.1016/j.jtauto.2025.100293","DOIUrl":"10.1016/j.jtauto.2025.100293","url":null,"abstract":"<div><h3>Background</h3><div>An epigenetic regulation of thrombo-inflammation has been reported in Behçet syndrome (BS), likely driven by a unique profile of three plasmatic circulating microRNAs (ci-miRNAs) (miR-206, miR-224-5p, and miR-653-5p). We compared this ci-miRNAs expression in BS and antiphospholipid syndrome (APS), the prototype of acquired pro-thrombotic autoimmune disease. To further corroborate the hypothesis that shared mechanisms drive the thrombotic process in BS and APS, we further assessed their thrombin generation assay (TGA) profile.</div></div><div><h3>Methods</h3><div>The three ci-miRNA expression was evaluated in 39 patients with BS, 33 with APS and 30 healthy controls (HCs). Single marker and combined ROC curve analyses were performed. TGA was conducted on pre-collected platelet poor plasma samples from 35 patients with BS and 77 with APS.</div></div><div><h3>Results</h3><div>The three ci-miRNAs, taken individually or combined, lacked acceptable discriminating power between groups [AUC from combiROC 0.64 (95 % CI: 0.51–0.78)]. Conversely, in the subgroups of BS and APS patients with vascular involvement (n = 22 each), the combined signature well discriminated between the two syndromes [AUC 0.83 (0.71–0.96), specificity 0.91, sensitivity 0.77], as well as between thrombotic APS and HCs [AUC 0.79 (0.64–0.91)]. Also, distinct trends in thrombograms emerged between BS and APS, with BS TGA displaying lower tLag and tPeak, higher Peak and similar AUC as compared to APS.</div></div><div><h3>Conclusions</h3><div>Despite shared elements in the ci-miRNA regulation of their pro-thrombotic tendency, distinct epigenetic factors seem to contribute to the pathogenesis of vascular events in BS and APS, possibly accounting also for the different global clotting assay observed in these diseases.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"11 ","pages":"Article 100293"},"PeriodicalIF":4.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212458","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":"Characteristics of polyclonal anti-interferon-gamma autoantibodies and novel diagnostic strategies: A prospective cohort study of new biomarkers","authors":"Xidong Wang ,&nbsp;Feng Ye ,&nbsp;Hongling Liu ,&nbsp;Shaoqiang Li ,&nbsp;Jinglu Yang ,&nbsp;Xue Yu ,&nbsp;Yilei Hui ,&nbsp;Yongming Li ,&nbsp;Yangqing Zhan ,&nbsp;Yan Wang ,&nbsp;Jing Liu ,&nbsp;Zhengtu Li","doi":"10.1016/j.jtauto.2025.100292","DOIUrl":"10.1016/j.jtauto.2025.100292","url":null,"abstract":"<div><h3>Background</h3><div><em>Anti</em>-γ interferon autoantibody (AIGA) syndrome is a widespread and grossly underestimated immunodeficiency disorder characterized by high mortality rates and a lack of standardized diagnostic methods. A highly accurate AIGA biomarker that meets the requirements of absolute quantification is urgently needed to enable the early diagnosis and treatment monitoring of the disease. In our study, we aimed to identify the primary components of AIGAs, determine their function, and develop a novel diagnostic method.</div></div><div><h3>Methods</h3><div>Immune repertoire sequencing and a retrospective antibody subtype index analysis were performed for typical patients. Affinity chromatography was used to isolate and purify IgGs from AIGAs in the plasma of AIGA(+) patients. The clinical application value of chromatography for testing AIGAs was evaluated in a prospective clinical cohort.</div></div><div><h3>Results</h3><div>A total of 114 eligible subjects were enrolled. Immune repertoire sequencing revealed that 74 % of the AIGA(+) patients had IgG clone types, with the somatic hypermutation (SHM) analysis being the most informative. We isolated AIGAs from the blood and interpreted their affinity and major components completely. Based on the results of this prospective cohort study, AIGAs, an absolute quantitative biomarker, were significantly better than the ELISA method (Delong test, P = 0.0018).</div></div><div><h3>Conclusions</h3><div>Patients with AIGA syndrome have abnormally elevated IgG levels, with IgG3 subtypes dominating. The disorder is characterized by the rapid acquisition of polyclonal AIGAs. The obtained AIGAs had a good neutralization capacity and potential as absolute quantitative biomarkers.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100292"},"PeriodicalIF":4.7,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071497","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":"2025-05-03","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":"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":"2025-05-02","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":"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":"2025-04-24","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":"The role of soluble CD40L in autoimmune diseases","authors":"Meryem Mabrouk ,&nbsp;Hicham Wahnou ,&nbsp;Yahye Merhi ,&nbsp;Haissam Abou-Saleh ,&nbsp;Fadila Guessous ,&nbsp;Younes Zaid","doi":"10.1016/j.jtauto.2025.100288","DOIUrl":"10.1016/j.jtauto.2025.100288","url":null,"abstract":"<div><div>CD40⁻CD40L is essential for immune system modulation because it coordinates both adaptive and inflammatory responses.</div><div>Systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, thrombocytopenic purpura, and rheumatoid arthritis are among the autoimmune illnesses in which it is especially prominent. Thus, the CD40⁻CD40L axis is a significant therapeutic target, despite the fact that its inhibition was first constrained by thromboembolic adverse effects.</div><div>New therapeutic approaches, such as nanotechnological methods and new-generation monoclonal antibodies, have been developed as a result of recent research with the goal of enhancing therapy efficacy and safety. This study opens up new avenues for the treatment of autoimmune illnesses by examining the pathophysiological consequences of CD40⁻CD40L and reviewing new treatments that target this pathway.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100288"},"PeriodicalIF":4.7,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851985","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":"Identification of autoantibodies targeting citrullinated CLEC12A in rheumatoid arthritis patients","authors":"Lillian Barra ,&nbsp;Sheri Saunders ,&nbsp;Mathias Mangion ,&nbsp;Guillaume Paré ,&nbsp;Halim Maaroufi ,&nbsp;Alain Garnier ,&nbsp;Ewa Cairns ,&nbsp;Maria J. Fernandes","doi":"10.1016/j.jtauto.2025.100287","DOIUrl":"10.1016/j.jtauto.2025.100287","url":null,"abstract":"<div><h3>Objective</h3><div>Rheumatoid arthritis is an autoimmune disease characterized by anti-citrullinated protein antibodies (ACPA). The pathogenic and protective roles of ACPA of distinct specificities are emerging and remains poorly understood. Thus, it is crucial to define the range of ACPA specificities and determine their contribution to disease and their potential clinical relevance. Since extracellular citrullination occurs in RA, we investigated whether autoantibodies in RA patients bind a citrullinated form of the cell-surface receptor CLEC12A that is expressed on neutrophils, the most abundant leukocyte in inflamed joints.</div></div><div><h3>Methods</h3><div>We generated a FLAG-tagged, recombinant form of the extracellular portion of human CLEC12A. After purification, the tag was removed prior to citrullination by PAD2 that was confirmed by mass spectrometry. We developed an ELISA for citrullinated CLEC12A to screen for seropositivity in sera of 68 RA patients and 36 healthy controls. Potential associations between these autoantibodies and clinical variables were determined.</div></div><div><h3>Results</h3><div>In our cohort, 40 % of RA patients were positive for anti-citrullinated CLEC12A autoantibodies. Those seropositive patients were younger than RA patients that tested negative for these autoantibodies (p = 0.0058). Most patients had antibodies to multiple citrullinated and homocitrullinated antigens; 17 % of patients negative for other ACPA were positive for anti-citrullinated CLEC12A autoantibodies.</div></div><div><h3>Conclusion</h3><div>This is the first report of seropositivity towards citrullinated CLEC12A in RA patients. A validation cohort will confirm our findings and identify additional correlations between these autoantibodies and clinical parameters. Citrullination may be a mechanism through which CLEC12A's inhibitory function is altered to exacerbate inflammation in RA. Identifying citrullinated neoantigens advances our understanding of the diverse molecular mechanisms that contribute to RA pathogenesis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100287"},"PeriodicalIF":4.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874692","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":"Leucine enhances the cGAS-STING-NLRP3 pathway in autoimmune thyroiditis","authors":"Xin Shen ,&nbsp;Tingting Feng ,&nbsp;Shangbin Li ,&nbsp;Xingxin Wang ,&nbsp;Wenhui Zhang ,&nbsp;Shouyan Wang ,&nbsp;Xiaohan Zhang ,&nbsp;Jiguo Yang ,&nbsp;Yuanxiang Liu","doi":"10.1016/j.jtauto.2025.100284","DOIUrl":"10.1016/j.jtauto.2025.100284","url":null,"abstract":"<div><h3>Background</h3><div>Branched-chain amino acids (BCAAs), including isoleucine (Ile), leucine (Leu), and valine (Val), are substrates for synthesising nitrogenous compounds and signalling molecules involved in regulating immunity. To date, data on the role of BCAAs in autoimmune thyroiditis (AIT) are lacking; therefore, this study aimed to determine the causality using two-sample Mendelian randomisation (MR) and explored the role of BCAAs in the cGAS-STING-NLRP3 pathway <em>in vitro</em>.</div></div><div><h3>Methods</h3><div>The causal relationship between BCAAs and the pathogenesis of AIT were identified using a two-sample MR study. The anti-inflammatory effects of BCAAs and their role in the cGAS-STING-NLRP3 pathway were investigated in lipopolysaccharide (LPS)- induced thyroid follicular cells (TFCs).</div></div><div><h3>Results</h3><div>Our findings indicate that BCAAs are a pathogenic factor for AIT (IVW OR = 4.960; 95 % CI = (1.54,15.940); <em>P</em> = 0.007). Leu significantly exacerbated the inflammatory response of thyroid cells, as evidenced by the up-regulation of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and down-regulation of TGF-β1; simultaneously aggravated cellular injury and oxidative stress; significantly increased the expression of Sestrin2/p-mTOR and cGAS/STING/NLRP3 in AIT cells. Furthermore, the expression of IL-18 and IL-1β was significantly increased. Conversely, Leu deprivation induced cell injury, decreased oxidative stress, and inhibited Sestrin2/p-mTOR and cGAS/STING/NLRP3 pathways.</div></div><div><h3>Conclusion</h3><div>Our findings suggest a potential causal effect of genetically predicted Leu on AIT; Leu significantly exacerbated the inflammatory response and cellular damage in AIT cells. The mechanism by which Leu induces inflammation involves activating the promoted Sestrin2/mTOR and cGAS-STING-NLRP3 signalling pathways. Our study proposes a novel mechanism for the contributions of Leu in AIT and potential therapeutic strategies involving Leu deprivation in treating AIT.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100284"},"PeriodicalIF":4.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706316","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}