Journal of Translational Autoimmunity最新文献

{"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}

{"title":"Association of COVID-19 with Thyroid Dysfunction and Autoimmune Thyroid Disease: A Retrospective Cohort Study","authors":"Jia Di ,&nbsp;Xiaodong Ma ,&nbsp;Tao Wu ,&nbsp;Eryue Qiao ,&nbsp;Mojtaba Salouti ,&nbsp;Yu Zhong ,&nbsp;Qian Xia ,&nbsp;Danfeng Kong ,&nbsp;Min Hao ,&nbsp;Qingwei Xie ,&nbsp;Zhuang Ge ,&nbsp;Dongzheng Liu ,&nbsp;Juanyi Feng ,&nbsp;Xianghong Zheng","doi":"10.1016/j.jtauto.2024.100255","DOIUrl":"10.1016/j.jtauto.2024.100255","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Since the end of the COVID-19 pandemic, the potential roles of thyroid-inflammatory derangements in driving or being associated with the prognosis of COVID-19 remain controversial. We aimed to clarify the association between COVID-19 infection and thyroid dysfunction, and highlight the impacts of subsequent autoimmune thyroid disease (AITD) on the prognosis of COVID-19.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The retrospective, multicenter, cohort study enrolled 2,339 participants with COVID-19 from three hospitals located in the north, middle, and south regions of Shaan Xi Province, China, between December 2022 and July 2023. 464 non-COVID-19 patients within the same period were supplemented, divided into groups with and without AITD. At hospital admission (baseline), 3- and 6-month follow-ups, we presented a dynamic description and correlation analysis of thyroid-inflammatory-autoimmune derangements in patients with AITD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 2,082 COVID-19 patients diagnosed with AITD and 257 cases without AITD were included in the study, and 464 non-COVID-19 patients were supplemented, dividing into 14 AITD and 450 non-AITD cases. We found that COVID-19 infection was closely associated with thyroid dysfunction (&lt;em&gt;χ&lt;/em&gt;&lt;sup&gt;&lt;em&gt;2&lt;/em&gt;&lt;/sup&gt; = 1518.129, &lt;em&gt;p&lt;/em&gt; = 0.000). AITD patients with COVID-19 showed a higher prevalence of symptoms and comorbidities and longer hospital stays at baseline than non-AITD patients with COVID-19 (&lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, and &lt;em&gt;p&lt;/em&gt; = 0.000). The baseline free triiodothyronine (FT3), free thyroxine, and radioactive iodine uptake at 24 hours in AITD cases significantly decreased (&lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, and &lt;em&gt;p&lt;/em&gt; = 0.000), while thyroid stimulating hormone, thyroglobulin, reverse triiodothyronine (rT3), and thyroid antibodies varying elevated from the baseline to the follow-up (baseline: &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, and &lt;em&gt;p&lt;/em&gt; = 0.000; 3-month follow-up: &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.030, and &lt;em&gt;p&lt;/em&gt; = 0.000). C-reactive protein, calcitonin, interleukin-6, -8, -10, and tumor necrosis factor-α rose significantly at baseline (&lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000, and &lt;em&gt;p&lt;/em&gt; = 0.000) in AITD. Interferon-α and interferon-γ at baseline showed a significant decrease (&lt;em&gt;p&lt;/em&gt; = 0.000 and &lt;em&gt;p&lt;/em&gt; = 0.000), and remained at low levels after 6 months (&lt;em&gt;p&lt;/em&gt; = 0.000 and &lt;em&gt;p&lt;/em&gt; = 0.000). FT3 and rT3 were positively and negatively correlated with hospitalization, respectively (&lt;em&gt;r&lt;/em&gt; = -0.208, 0.231; &lt;em&gt;p&lt;/em&gt; = 0.000, &lt;em&gt;p&lt;/em&gt; = 0.000). ROC curves showed that FT3 and rT3 had better robustness in predicting severe COVID-19 prognosis (AUC = 0.801, 0.705). Ordered logistic regression revealed that ORs were","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100255"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527347","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":"Airborne culprits: A comprehensive review of PM, silica, and TCDD in autoimmune diseases","authors":"Daniel Galeano-Sánchez,&nbsp;Victoria Morales-González,&nbsp;Diana M. Monsalve,&nbsp;Carolina Ramırez-Santana,&nbsp;Yeny Acosta-Ampudia","doi":"10.1016/j.jtauto.2024.100253","DOIUrl":"10.1016/j.jtauto.2024.100253","url":null,"abstract":"<div><div>Autoimmune diseases (ADs) are immunological disorders arising from the breakdown of immune tolerance, influenced by various internal and external factors. Persistent exposure to environmental factors, particularly air pollution, is linked to systemic inflammation, oxidative stress, and apoptosis, which contribute to the development of ADs.</div><div>This review examines the impact of air pollutants, including particulate matter, silica, and TCDD, by analyzing epidemiological studies, animal models, and <em>in vitro</em> assays. It focuses on how air pollution disrupts the immune system, leading to apoptosis, increased oxidative stress, cytokine production, autoantigen release, autoantibody production, and autoreactivity, which are particularly significant in ADs like rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, and systemic sclerosis. In essence, this approach aims to provide a profound understanding of how exposure to air pollution can initiate or contribute to ADs, offering potential avenues for more targeted preventive and therapeutic strategies.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100253"},"PeriodicalIF":4.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432724","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":"Extrafollicular CD19lowCXCR5−CD11c− double negative 3 (DN3) B cells are significantly associated with disease activity in females with systemic lupus erythematosus","authors":"Carlo Chizzolini ,&nbsp;Jean-Charles Guery ,&nbsp;Fanny Noulet ,&nbsp;Lyssia Gruaz ,&nbsp;Claire Cenac ,&nbsp;Loredana Frasca ,&nbsp;David Spoerl ,&nbsp;Lionel Arlettaz ,&nbsp;Alice Horisberger ,&nbsp;Camillo Ribi ,&nbsp;Stéphanie Hugues","doi":"10.1016/j.jtauto.2024.100252","DOIUrl":"10.1016/j.jtauto.2024.100252","url":null,"abstract":"<div><h3>Objective</h3><div>B cells play a major role in the development and maintenance of systemic lupus erythematosus (SLE). Double negative (DN) B cells defined by the lack of surface expression of IgD and CD27 have attracted recent interest for their sensitivity to Toll-like receptor 7 (TLR7) ligands and their potential role in the production of autoantibodies. Here we aimed at investigating the possible association of DN B cells and their subsets with SLE disease activity specifically in female patients, in which TLR7 gene has been reported to escape X chromosome inactivation.</div></div><div><h3>Methods</h3><div>Peripheral blood mononuclear cells were purified from woman participating to the clinically well-characterized Swiss SLE Cohort Study (SSCS). PBMC from age-matched healthy females were used as controls. PBMC were stained for cell surface markers, intracellular Tbet and analyzed by multicolor cytofluorimetry. Single nucleotide TLR7 polymorphisms were assessed by polymerase chain reaction.</div></div><div><h3>Results</h3><div>The median SLE disease activity index of the 86 females was 2, IQR [0–6], all but 8 were under chronic SLE treatment. B cells co-expressing CD11c and Tbet were increased, the mean fluorescence intensity (MFI) of CD19 was considerably reduced and we observed a large increase in CD11c + CXCR5-and CD11c-CXCR5-concomitantly with a reduction of CD11c-CXCR5+ B cells in SLE compared to 40 healthy donors (HD). When focusing on the DN B cell subset, we found a reduction of DN1 (CD11c-CXCR5+) and an increase of DN2 (CD11c + CXCR5-) and most impressively of DN3 (CD11c-CXCR5-) cells. The DN subset, particularly DN3, showed the lowest level of CD19 expression. Both DN1 and DN3 percentages as well as the CD19 MFI of DN cells were associated with SLE disease activity. The use of glucocorticoids, immunosuppressants, and antimalarials impacted differentially on the frequencies of DN B cell subsets. CD19 MFI in B cells and the percentage of DN3 were the strongest biomarkers of disease activity. The TLR7 snp3858384 G allele was associated with increased percentages of B cells and CD19⁺CD11c-CXCR5+ and decreased CD19⁺CD11c-CXCR5-.</div></div><div><h3>Conclusions</h3><div>DN3 B cells are strongly associated with SLE clinical activity pointing to their potential involvement in disease pathogenesis, and CD19 expression level performs accurately as disease activity biomarker.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100252"},"PeriodicalIF":4.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427002","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":"Mitochondrial DNA copy number and the risk of autoimmune diseases: A Mendelian randomization study with meta-analysis","authors":"Mingzhu Liu ,&nbsp;Xiongquan Long ,&nbsp;Shuangshuang Fu ,&nbsp;Yuyang Zhang ,&nbsp;Zihao Liu ,&nbsp;Xiaoping Xu ,&nbsp;Minghao Wu","doi":"10.1016/j.jtauto.2024.100251","DOIUrl":"10.1016/j.jtauto.2024.100251","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial DNA plays a crucial role in the pathophysiology of autoimmune diseases (ADs). However, the association between mitochondrial DNA copy number (mtDNA-CN) and ADs risk is controversial. In this study, Mendelian randomization (MR) analysis and meta-analysis were performed using three sets of independent instrumental variables (IVs) to investigate the potential association between mtDNA-CN and 20 types of ADs.</div></div><div><h3>Methods</h3><div>The three sets of IVs were drawn primarily from participants in the UK Biobank and the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium using different methods. Outcome data for ADs were investigated using summary statistics from the FinnGen cohort. The potential causal associations were assessed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. Sensitivity analysis and the Steiger test were used to verify the robustness of the MR estimates. In addition, a meta-analysis was conducted to pool the results from three IV groups.</div></div><div><h3>Results</h3><div>Overall, genetically predicted mtDNA-CN was not associated with ADs risk (OR = 1.046, 95 % CI: 0.964–1.135, P = 0.283). However, subgroup analyses showed positive causal associations of mtDNA-CN with autoimmune hypothyroidism (OR = 1.133, 95 % CI: 1.016–1.262, P = 0.024) and rheumatoid arthritis (OR = 1.219, 95 % CI: 1.028–1.445, P = 0.023). In contrast, there was no causal association between mtDNA-CN and atopic dermatitis as well as psoriasis, ulcerative colitis, adult-onset Still disease, type1 diabetes, Crohn disease, sarcoidosis, ankylosing spondylitis, multiple sclerosis, autoimmune hyperthyroidism, primary sclerosing cholangitis, systemic lupus erythematosus, systemic sclerosis, alopecia areata, myasthenia gravis, Guillain-Barre syndrome, dermatopolymyositis, and vitiligo.</div></div><div><h3>Conclusions</h3><div>This MR analysis showed mtDNA-CN is causally associated with an increased risk of autoimmune hypothyroidism and rheumatoid arthritis at the genetic level. The findings have important implications for the use of mtDNA-CN as a biomarker for risk assessment of autoimmune hypothyroidism and rheumatoid arthritis in clinical practice.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100251"},"PeriodicalIF":4.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427001","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":"Vascular injury derived apoptotic exosome-like vesicles trigger autoimmunity","authors":"Sandrine Juillard ,&nbsp;Annie Karakeussian-Rimbaud ,&nbsp;Marie-Hélène Normand ,&nbsp;Julie Turgeon ,&nbsp;Charlotte Veilleux-Trinh ,&nbsp;Alexa C. Robitaille ,&nbsp;Joyce Rauch ,&nbsp;Andrzej Chruscinski ,&nbsp;Nathalie Grandvaux ,&nbsp;Éric Boilard ,&nbsp;Marie-Josée Hébert ,&nbsp;Mélanie Dieudé","doi":"10.1016/j.jtauto.2024.100250","DOIUrl":"10.1016/j.jtauto.2024.100250","url":null,"abstract":"<div><p>According to a central tenet of classical immune theory, a healthy immune system must avoid self-reactive lymphocyte clones but we now know that B cells repertoire exhibit some level of autoreactivity. These autoreactive B cells are thought to rely on self-ligands for their clonal selection and survival. Here, we confirm that healthy mice exhibit self-reactive B cell clones that can be stimulated <em>in vitro</em> by agonists of toll-like receptor (TLR) 1/2, TLR4, TLR7 and TLR9 to secrete anti-LG3/perlecan. LG3/perlecan is an antigen packaged in exosome-like structures released by apoptotic endothelial cells (ApoExos) upon vascular injury. We demonstrate that the injection of ApoExos in healthy animals activates the IL-23/IL-17 pro-inflammatory and autoimmune axis, and produces several autoantibodies, including anti-LG3 autoantibodies and hallmark autoantibodies found in systemic lupus erythematosus. We also identify γδT cells as key mediators of the maturation of ApoExos-induced autoantibodies in healthy mice. Altogether we show that ApoExos released by apoptotic endothelial cells display immune-mediating functions that can stimulate the B cells in the normal repertoire to produce autoantibodies. Our work also identifies TLR activation and γδT cells as important modulators of the humoral autoimmune response induced by ApoExos.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100250"},"PeriodicalIF":4.7,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000200/pdfft?md5=10a63c2cb5c64a890726d7f77c3163c6&pid=1-s2.0-S2589909024000200-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095934","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":"Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus","authors":"Bing Wang,&nbsp;Biqing Zhang,&nbsp;Min Wu,&nbsp;Ting Xu","doi":"10.1016/j.jtauto.2024.100249","DOIUrl":"10.1016/j.jtauto.2024.100249","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE) represents an autoimmune disorder that affects multiple systems. In the treatment of this condition, the focus primarily revolves around inflammation suppression and immunosuppression. Consequently, targeted therapy has emerged as a prevailing approach. Currently, the quest for highly sensitive and specifically effective targets has gained significant momentum in the context of SLE treatment. Lymphocyte activation gene-3 (LAG-3) stands out as a crucial inhibitory receptor that binds to pMHC-II, thereby effectively dampening autoimmune responses. Fibrinogen-like protein 1 (FGL1) serves as the principal immunosuppressive ligand for LAG-3, and their combined action demonstrates a potent immunosuppressive effect. This intricate mechanism paves the way for potential SLE treatment by targeting LAG-3 with FGL1. This work provides a comprehensive summary of LAG-3's role in the pathogenesis of SLE and elucidates the feasibility of leveraging FGL1 as a therapeutic approach for SLE management. It introduces a novel therapeutic target and opens up new avenues of therapeutic consideration in the clinical context of SLE treatment.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100249"},"PeriodicalIF":4.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000194/pdfft?md5=9ede3dcb5f11d159f2702ec556ac9231&pid=1-s2.0-S2589909024000194-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841524","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":"Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome","authors":"Jun Huang ,&nbsp;Jia Tang ,&nbsp;Chen Zhang,&nbsp;Tingting Liu,&nbsp;Zhiyong Deng,&nbsp;Lei Liu","doi":"10.1016/j.jtauto.2024.100248","DOIUrl":"10.1016/j.jtauto.2024.100248","url":null,"abstract":"<div><h3>Objective</h3><p>Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease.</p></div><div><h3>Methods</h3><p>Single-cell RNA sequencing (scRNA-seq) was performed on 32,337 cells of labial glands from three pSS patients and three healthy individuals. We analyzed all cell subsets implicated in pSS pathogenesis.</p></div><div><h3>Results</h3><p>Our research revealed diminished differentiation among epithelial cells, concomitant with an enhancement of interferons (IFNs)-mediated signaling pathways. This indicates a cellular functional shift in reaction to inflammatory triggers. Moreover, we observed an augmentation in the population of myofibroblasts and endothelial cells, likely due to the intensified IFNs signaling, suggesting a possible reconfiguration of tissue structure and vascular networks in the impacted regions. Within the immune landscape, there was an apparent increase in immunosuppressive macrophages and dendritic cells (DCs), pointing to an adaptive immune mechanism aimed at modulating inflammation and averting excessive tissue harm. Elevated activation levels of CD4⁺T cells, along with a rise in regulatory T (Treg) cells, were noted, indicating a nuanced immune interplay designed to manage the inflammatory response. In the CD8⁺T cell subsests, we detected a notable increase in cells expressing granzyme K (GZMK), signaling an intensified cytotoxic activity. Additionally, the escalated presence of T cells with high levels of heat shock proteins (HSPs) suggests a cellular stress condition, possibly associated with persistent low-grade inflammation, mirroring the chronic aspect of the condition.</p></div><div><h3>Conclusions</h3><p>Our research identified distinct stromal and immune cell populations linked to pSS, revealing new potential targets for its management. The activation of myeloid, B, and T cells could contribute to pSS pathogenesis, providing important guidance for therapeutic approaches.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100248"},"PeriodicalIF":4.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000182/pdfft?md5=28c94a7aa08c4484edc759073e98b10c&pid=1-s2.0-S2589909024000182-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141701616","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":"To switch or to swap? Evidence from a meta-analysis for the best treatment approach in childhood chronic uveitis resistant to the I anti-TNF","authors":"Ilaria Maccora ,&nbsp;Sara Soldovieri ,&nbsp;Teodoro Oliverio ,&nbsp;Salvatore de Masi ,&nbsp;Edoardo Marrani ,&nbsp;Ilaria Pagnini ,&nbsp;Maria Vincenza Mastrolia ,&nbsp;Gabriele Simonini","doi":"10.1016/j.jtauto.2024.100247","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100247","url":null,"abstract":"<div><h3>Objective</h3><p>Since adalimumab approval in childhood chronic non-infectious uveitis (cNIU), the prognosis has been dramatically changed, but the 25 % failed to achieve inactivity. There is not accordance if it is better to switch to another anti-TNF or to swap to another category of biologic. Thus, we aim to summarize evidence regarding the best treatment of cNIU refractory to the first anti-TNF.</p></div><div><h3>Methods</h3><p>A systematic literature review and meta-analysis, according to PRISMA Guidelines, was performed(Jan2000-Aug2023). Studies investigating the efficacy of treatment in cNIU refractory to the first anti-TNF were considered for inclusion. The primary outcome was the improvement of intraocular inflammation according to SUN. A combined estimation of the proportion of children responding to switch or swap and for each drug was performed.</p></div><div><h3>Results</h3><p>23 articles were eligible, reporting 150 children of whom 109 switched anti-TNF (45 adalimumab, 49 infliximab, 9 golimumab) and 41 swapped to another biologics (31 abatacept, 8 tocilizumab and 1 rituximab). The proportion of responding children was 46 %(95 % CI 23-70) for switch and 38 %(95 % CI 8-73) for swap (χ²0.02, p = 0.86). Instead analysing for each drug, the proportion of responding children was the 24 %(95 % CI 2-55) for adalimumab, 43 %(95 % CI 2-80) for abatacept, 79 %(95 % CI 61-93) for infliximab, 56 %(95 % CI 14-95) for golimumab and 96 %(95 % CI 58-100) for tocilizumab. We evaluated a superiority of tocilizumab and infliximab compared to the other drugs(χ² 27.5 p &lt; 0.0001).</p></div><div><h3>Conclusion</h3><p>Although non-conclusive, this meta-analysis suggests that, after the first anti-TNF failure, tocilizumab and infliximab are the best available treatment for the management of cNIU.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"9 ","pages":"Article 100247"},"PeriodicalIF":4.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000170/pdfft?md5=0c91f958902d6a7d2c337e34d2d6fdd5&pid=1-s2.0-S2589909024000170-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141487571","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}