Journal of Translational Autoimmunity最新文献

{"title":"Cellular therapies in rheumatic and musculoskeletal diseases","authors":"Pedro Franco-Fuquen ,&nbsp;Juana Figueroa-Aguirre ,&nbsp;David A. Martínez ,&nbsp;Eider F. Moreno-Cortes ,&nbsp;Juan E. Garcia-Robledo ,&nbsp;Fabio Vargas-Cely ,&nbsp;Daniela A. Castro-Martínez ,&nbsp;Mustafa Almaini ,&nbsp;Januario E. Castro","doi":"10.1016/j.jtauto.2024.100264","DOIUrl":"10.1016/j.jtauto.2024.100264","url":null,"abstract":"<div><div>A substantial proportion of patients diagnosed with rheumatologic and musculoskeletal diseases (RMDs) exhibit resistance to conventional therapies or experience recurrent symptoms. These diseases, which include autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, are marked by the presence of autoreactive B cells that play a critical role in their pathogenesis. The persistence of these autoreactive B cells within lymphatic organs and inflamed tissues impairs the effectiveness of B-cell-depleting monoclonal antibodies like rituximab.</div><div>A promising therapeutic approach involves using T cells genetically engineered to express chimeric antigen receptors (CARs) that target specific antigens. This strategy has demonstrated efficacy in treating B-cell malignancies by achieving long-term depletion of malignant and normal B cells. Preliminary data from patients with RMDs, particularly those with lupus erythematosus and dermatomyositis, suggest that CAR T-cells targeting CD19 can induce rapid and sustained depletion of circulating B cells, leading to complete clinical and serological responses in cases that were previously unresponsive to conventional therapies.</div><div>This review will provide an overview of the current state of preclinical and clinical studies on the use of CAR T-cells and other cellular therapies for RMDs. Additionally, it will explore potential future applications of these innovative treatment modalities for managing patients with refractory and recurrent manifestations of these diseases.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100264"},"PeriodicalIF":4.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174020","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":"IL-12 family cytokines and autoimmune diseases: A potential therapeutic target?","authors":"Xiaoyu Cui ,&nbsp;Wu Liu ,&nbsp;Hanxue Jiang ,&nbsp;Qihan Zhao ,&nbsp;Yuehong Hu ,&nbsp;Xinyue Tang ,&nbsp;Xianli Liu ,&nbsp;Haoran Dai ,&nbsp;Hongliang Rui ,&nbsp;Baoli Liu","doi":"10.1016/j.jtauto.2024.100263","DOIUrl":"10.1016/j.jtauto.2024.100263","url":null,"abstract":"<div><div>In recent years, the discovery of IL-12 family cytokines, which includes IL-12, IL-23, IL-27, IL-35, and IL-39, whose biological functions directly or indirectly affect various autoimmune diseases. In autoimmune diseases, IL-12 family cytokines are aberrantly expressed to varying degrees. These cytokines utilize shared subunits to influence T-cell activation and differentiation, thereby regulating the balance of T-cell subsets, which profoundly impacts the onset and progression of autoimmune diseases. In such conditions, IL-12 family members are aberrantly expressed to varying degrees. By exploring their immunomodulatory functions, researchers have identified varying therapeutic potentials for each member. This review examines the physiological functions of the major IL-12 family members and their interactions, discusses their roles in several autoimmune diseases, and summarizes the progress of clinical studies involving monoclonal antibodies targeting IL-12 and IL-23 subunits currently available for treatment.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100263"},"PeriodicalIF":4.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932900","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":"Development of a standardized monoclonal antibody to the inner lipoyl domain of PDC-E2 as a potential international AMA reference","authors":"Zhuye Qin ,&nbsp;Fangming Cheng ,&nbsp;Mingming Zhang ,&nbsp;Ruonan Qian ,&nbsp;Hong Chen ,&nbsp;Yaqin Zhao ,&nbsp;Youtao Zhang ,&nbsp;Yaping Dai ,&nbsp;Chaochao Tang ,&nbsp;Peng Jiang ,&nbsp;Xiaoli Hua ,&nbsp;Shen Li ,&nbsp;Bing Zheng ,&nbsp;Pin Yu ,&nbsp;Xingjuan Shi ,&nbsp;Suraj Timilsina ,&nbsp;M. Eric Gershwin ,&nbsp;Xiangdong Liu ,&nbsp;Chungen Qian ,&nbsp;Fang Qiu","doi":"10.1016/j.jtauto.2024.100262","DOIUrl":"10.1016/j.jtauto.2024.100262","url":null,"abstract":"<div><div>The detection of antimitochondrial antibodies (AMA) is the specific diagnostic marker for primary biliary cholangitis. Indeed, it is the most specific autoantibody in clinical autoimmunity, with a high titer directed response to the inner lipoyl domain of PDC-E2. The current international reference for AMA detection is based upon sera samples of PBC patients. In rheumatic diseases, i.e. rheumatoid arthritis, great efforts are placed at development of international standards. In this study, we report the development of a monoclonal chimeric IgG1 antibody as a reference for AMA testing. A monoclonal 4G6 antibody was constructed from a murine monoclonal antibody specific for the inner lipoyl domain (ILD) of PDC-E2, by combining the variable region with the constant region of human IgG1. The 4G6 antibody recognizes all AMA epitopes containing the ILD of PDC-E2, including the classical BPO recombinant antigen in all currently available diagnostic methods. The binding affinity of the 4G6 antibody to PDC-E2 and BPO antigen reaches <em>K</em>_D value of 7.22 × 10⁻¹¹ M and 4.55 × 10⁻¹¹ M, which is sufficient to use as a quantitative reference for all AMA tests. The unlimited availability of the 4G6 antibody makes it a promising candidate for use as an AMA reference or assay calibrator for the international community.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100262"},"PeriodicalIF":4.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698963","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":"Prognostic value of β1 adrenergic receptor autoantibodies for microvascular obstruction in patients with STEMI with Post-PCI: A prospective cohort study","authors":"Ning Cao ,&nbsp;Wenxi Dang ,&nbsp;Yanguo Xin ,&nbsp;Jiayu Li ,&nbsp;Shaohua Guo ,&nbsp;Qitian Li ,&nbsp;Hui Chen ,&nbsp;Shun Li","doi":"10.1016/j.jtauto.2024.100261","DOIUrl":"10.1016/j.jtauto.2024.100261","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Coronary microvascular obstruction (MVO) frequently occurs in patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI), leading to poor prognosis. β₁ adrenergic receptor autoantibodies (β₁-AA) are present in various cardiovascular diseases and correlate with cardiac damage and dysfunction. However, whether β₁-AA is associated with the occurrence of MVO in patients with STEMI after PCI remains unclear.</div></div><div><h3>Aims</h3><div>To investigate the prognostic relationship between β₁-AA and the occurrence of MVO in patients with STEMI with post-PCI.</div></div><div><h3>Methods</h3><div>This prospective study included 403 patients with STEMI who underwent primary PCI. The patients were divided into MVO+ and MVO- groups. Serum β₁-AA levels were measured prior to primary PCI. The primary outcome was MVO, assessed through cardiac magnetic resonance imaging at 5–7 days after PCI.</div></div><div><h3>Results</h3><div>A total of 127 MVO+ and 276 MVO– patients were identified. Patients with MVO + exhibited higher β₁-AA optical density (OD) compared to MVO- patients. β₁-AA OD, pNT-proBNP, pCK-MB and pTNI were positively associated with MVO following PCI. Notably, the assocition between β₁-AA levels and MVO risk strengthened with increasing pNT-proBNP levels. The combination of β₁-AA, pNT-proBNP and pTNI yielded the most efficient MVO prediction with an area under the ROC curve of 0.87 (95 % CI: 0.83–0.90).</div></div><div><h3>Conclusions</h3><div>β₁-AA is significantly associated with the occurrence of MVO in STEMI patients following primary PCI. The combination of β₁-AA with pNT-proBNP and pTNI improves predictive accuracy, providing a more robust and effective strategy for assessing MVO risk.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100261"},"PeriodicalIF":4.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661280","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":"Dissecting the genetic basis and mechanisms underlying the associations between multiple extrahepatic factors and autoimmune liver diseases","authors":"Zheng Zhang ,&nbsp;Jiayi Zhang ,&nbsp;Xinyang Yan ,&nbsp;Jiachen Wang ,&nbsp;Haoxiang Huang ,&nbsp;Menghao Teng ,&nbsp;Qingguang Liu ,&nbsp;Shaoshan Han","doi":"10.1016/j.jtauto.2024.100260","DOIUrl":"10.1016/j.jtauto.2024.100260","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune liver diseases (AILDs) encompass autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The onset of these diseases is fundamentally influenced by genetic susceptibility. Although various extrahepatic factors are potentially linked to AILDs, the genetic underpinnings and mechanisms of these associations remain unclear.</div></div><div><h3>Methods</h3><div>Utilizing large-scale genome-wide association study (GWAS) data, this study systematically investigated the relationships between extrahepatic autoimmune diseases (EHAIDs), immune cells, and various triggering factors with AILDs. Mendelian randomization (MR) was employed to assess the causal effects of these extrahepatic factors on AILDs, complemented by linkage disequilibrium score (LDSC) regression to uncover shared genetic architecture and causal effects underlying the associations between autoimmune diseases. We employed colocalization, enrichment analysis, and protein-protein interaction (PPI) network to identify the functions of shared loci. Additionally, we proposed that activated immune cells in the circulation may contribute to liver and biliary tract inflammation via migration, mediating the impact of extrahepatic factors on AILDs. This hypothesis was tested using two mediation analysis methods: two-step MR (TSMR) and multivariable MR (MVMR).</div></div><div><h3>Results</h3><div>Causal associations between multiple extrahepatic factors and AILDs were identified. Notably, CD27⁺ B cells were found to be a risk factor for PBC, while PSC progression was associated with CD28⁺ CD8⁺ T cells exhaustion and increased levels of CD28⁻ CD8⁺ T cells. Mediation analyses revealed 64 pathways via TSMR and 15 pathways via MVMR, indicating that the effects of extrahepatic factors on AILDs may be mediated by circulating immune cells. The shared genetic architecture also contributed to these associations. Analysis of shared loci and gene functions identified ATXN2 as being shared between PBC and 9 EHAIDs, while SH2B3 and PSMG1 were shared with 6 and 5 EHAIDs, respectively, in PSC.</div></div><div><h3>Conclusions</h3><div>Our research compared three distinct AILDs, enhancing the understanding of their etiology and providing new evidence on risk factors, diagnostic markers, and potential therapeutic targets.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100260"},"PeriodicalIF":4.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915847","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 interplay between epidermal barrier distribution, microbiota composition, and immune infiltrate defines and stratifies psoriasis patients and is associated with disease severity","authors":"Elizabeth M. Ortega Rocha ,&nbsp;Paul Hernández-Herrera ,&nbsp;Sofia V. de los Santos- Carmona ,&nbsp;Saraí G De León-Rodríguez ,&nbsp;Ángel Juárez-Flores ,&nbsp;Vadim Pérez-Koldenkova ,&nbsp;Octavio Castro-Escamilla ,&nbsp;Samira Muñoz-Cruz ,&nbsp;Alicia Lemini-López ,&nbsp;Laura C. Bonifaz","doi":"10.1016/j.jtauto.2024.100257","DOIUrl":"10.1016/j.jtauto.2024.100257","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory autoimmune skin disease characterized by keratinocyte hyperproliferation, primarily driven by the IL-23/IL-17 axis. In addition to immune response, various skin components, including the epidermal barrier and the skin microbiota, have been individually implicated in the disease pathogenesis. Here, we aimed to investigate the interplay between epidermal tight junctions, Staphylococcus aureus enterotoxin B (SEB), and CD4 T cell-mediated immune responses. By immunofluorescence analyses of skin biopsies, we observed that claudin-1 distribution was significantly altered in psoriatic patients, which correlated with the localization of <em>Staphylococcus aureus</em> and SEB across skin layers and with disease severity. Furthermore, functional CD4 TCRvβ17 cells were associated with SEB presence in patients skin and positively correlated with psoriasis severity. Notably, in patients with SEB detected in the dermis, CD4 TCRvβ17 IL-17 cells were linked to barrier abnormalities.</div><div>Unsupervised analysis stratified psoriasis patients into three groups based on SEB presence and location, supporting the previous findings. The patient group with SEB in the dermis exhibited improved responses to biological therapy, including reductions in PASI score, claudin-1 fragmentation, <em>S. aureus</em> and SEB presence, and CD4 TCRvβ17 cell percentages. Our findings emphasize the complex interplay between epidermal barrier distribution, SEB localization, and functional CD4 TCRvβ17 cells in psoriatic skin, highlighting their potential in patient stratification in association with the severity of the disease.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100257"},"PeriodicalIF":4.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142661141","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":"Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions","authors":"Yulin Bao ,&nbsp;Lingfeng Gu ,&nbsp;Jiayi Chen ,&nbsp;Hao Wang ,&nbsp;Zemu Wang ,&nbsp;Huijuan Wang ,&nbsp;Sibo Wang ,&nbsp;Liansheng Wang","doi":"10.1016/j.jtauto.2024.100259","DOIUrl":"10.1016/j.jtauto.2024.100259","url":null,"abstract":"<div><h3>Backgroud</h3><div>Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required.</div></div><div><h3>Results</h3><div>We assessed the impact of 19 common AIDs on 14 CVDs using bidirectional Mendelian randomization (MR). Celiac disease (odds ratio [OR] = 2.949, 95 % confidence interval [CI]: 1.111–7.827, P = 0.030) and type 1 diabetes mellitus (T1DM) (OR = 1.044, 95 % CI: 1.021–1.068, P = 1.82e-4) were associated with an increased risk of peripheral arterial disease (PAD). Additionally, celiac disease was linked to an increased risk of arrhythmia (OR = 1.008, 95 % CI: 1.002–1.013, P = 0.004), multiple sclerosis to venous thromboembolism (OR = 1.001, 95 % CI: 1.000–1.001, P = 0.010), and psoriasis to heart failure (OR = 1.048, 95 % CI: 1.021–1.077, P = 0.001). Sensitivity analyses were conducted to enhance the robustness of these findings. Predominantly, immune response and inflammation-related pathways were enriched in the aforementioned associations. Mediation analysis identified human leukocyte antigen-DR positive myeloid dendritic cells as partially mediating the effect of T1DM on PAD, with a mediated proportion of 16.61 % (P = 0.028). Potential therapeutic agents, such as tumor necrosis factor-alpha inhibitors and interferon, may have efficacy in treating AID-related CVDs.</div></div><div><h3>Conclusions</h3><div>This study presents genetic evidence of certain AIDs impacting specific CVDs and identifies potential mediators and drugs.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100259"},"PeriodicalIF":4.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572346","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":"Homeostatic signals, including IL-7 and self-MHC recognition, induce the development of peripheral helper T cells, which are enriched in the joints of rheumatoid arthritis","authors":"Ryosuke Tsurui ,&nbsp;Hisakata Yamada ,&nbsp;Takahiro Natori ,&nbsp;Motoki Yoshimura ,&nbsp;Yukio Akasaki ,&nbsp;Shinya Kawahara ,&nbsp;Hiroaki Niiro ,&nbsp;Yuya Kunisaki ,&nbsp;Yasuharu Nakashima","doi":"10.1016/j.jtauto.2024.100258","DOIUrl":"10.1016/j.jtauto.2024.100258","url":null,"abstract":"<div><h3>Objective</h3><div>Dysregulated T cell homeostasis has long been implicated in the pathogenesis of rheumatoid arthritis (RA), in the joint of which peripheral helper T (Tph) cells accumulate and form ectopic lymphoid organs. We examined whether homeostatic signals are involved in the development of Tph cells.</div></div><div><h3>Methods</h3><div>Human peripheral blood mononuclear cells were cultured with IL-7, the critical cytokine for T cell homeostasis. Development of Tph-like cells was assessed by flow cytometry, gene expression, and functional analysis. Chemotaxis of the Tph-like cells to RA synovial fluid (RASF) and the effect of RASF on the development of Tph-like cells was examined.</div></div><div><h3>Results</h3><div>PD-1^highCXCR5^- Tph-like cells developed from human peripheral blood CD4 T cells after proliferation in response to IL-7. Signals from self-MHC recognition and CD28 co-stimulation were also involved. The IL-7-induced Tph-like (IL-7-Tph) cells produced CXCL13 and IL-21 and helped B cells produce IgG. Comprehensive gene expression analysis further supported the similarity with Tph cells in RA joint. IL-7-Tph cells exhibited chemotaxis toward synovial fluid from RA patients (RASF), and RASF promoted the development of IL-7-Tph cells, which were also induced from CD4 T cells residing in non-inflamed joints.</div></div><div><h3>Conclusions</h3><div>Our results demonstrate an antigen-nonspecific developmental pathway of Tph cells triggered by homeostatic signals and promoted by the local environment of RA, which accounts for the accumulation of Tph cells in inflamed joints.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100258"},"PeriodicalIF":4.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572345","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":"C3 glomerulopathy is highly prevalent in French Polynesia","authors":"Nelly Candela ,&nbsp;Nicolas Benichou ,&nbsp;Mathilde Lefebvre ,&nbsp;Lorraine Gueguen ,&nbsp;Paula Vieira-Martins ,&nbsp;Carine El Sissy ,&nbsp;Hervé Sartelet ,&nbsp;Pascale Testevuide ,&nbsp;Ronan Delaval ,&nbsp;Stanislas Faguer","doi":"10.1016/j.jtauto.2024.100254","DOIUrl":"10.1016/j.jtauto.2024.100254","url":null,"abstract":"<div><h3>Objective</h3><div>To compare the natural history of C3 glomerulopathy (C3G) to acute post-infectious glomerulonephritis (APIGN) in a cohort of patients with a relative homogeneity of environment conditions and genetic background.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed the characteristics of all patients with biopsy proven C3G or APIGN referred in 2013–2019 to the only renal unit in French Polynesia.</div></div><div><h3>Results</h3><div>Point prevalence of C3G is ∼23 cases per 100,000 inhabitants. A recurrent variation of CFI (p.Arg406His) was identified at the heterozygous state in 4/8 (50 %) patients with C3G but its pathogenicity remain elusive. Characteristics at presentation and kidney outcomes were roughly similar between C3G (n = 16) and APIGN (n = 20), excepted for the presence of humps on kidney biopsy.</div></div><div><h3>Conclusions</h3><div>C3G is highly prevalent in French Polynesia suggesting specific genetic or environmental susceptibility factors. Systematic diagnosis workflow should be proposed to all patients with C3 predominant glomerulonephritis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100254"},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572347","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":"Integrated analysis of multi-omics data for the discovery of biomarkers and therapeutic targets for juvenile idiopathic arthritis","authors":"Yi-Xin Cai ,&nbsp;Xiao-Li Chen ,&nbsp;Dai-Shan Zheng ,&nbsp;Yue-Zhong Huang ,&nbsp;Zhan-Pei Bai ,&nbsp;Xiu-Feng Huang","doi":"10.1016/j.jtauto.2024.100256","DOIUrl":"10.1016/j.jtauto.2024.100256","url":null,"abstract":"<div><h3>Background</h3><div>Juvenile idiopathic arthritis (JIA) is a prevalent chronic rheumatic disease affecting children. Current medications merely alleviate symptoms rather than curing the disease. Hence, the identification and development of novel drug targets and biomarkers for JIA are imperative for enhancing treatment efficacy.</div></div><div><h3>Methods</h3><div>We employed two-sample Mendelian randomization (MR) analysis to investigate the causal effects of plasma proteins on JIA. Additionally, colocalization, bulk RNA-seq, and single-cell RNA-seq analyses were conducted to further investigate and validate the potential of candidate proteins as drug targets.</div></div><div><h3>Results</h3><div>Through MR analysis, we successfully identified five plasma proteins that are causally linked to JIA. Genetically inferred lower levels of AIF1, TNF, and TNFSF11 were associated with an elevated risk of JIA, while higher levels of AGER and GP1BA proteins were positively correlated with JIA risk. Colocalization analysis further supported our findings on GP1BA (OR = 9.26, 95 % CI: 2.30–37.20) and TNFSF11 (OR = 0.18, 95 % CI: 0.07–0.45). Based on this evidence, we classified these five proteins into two tiers. Finally, we conducted a systematic evaluation of the druggability and current drug development progress for these identified candidate proteins.</div></div><div><h3>Conclusions</h3><div>This study employed MR analysis to reveal causal relationships between plasma proteins and JIA, identifying five potential candidate proteins as promising drug targets for JIA, particularly focusing on GP1BA and TNFSF11.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100256"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142572348","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}