Journal of Translational Autoimmunity最新文献

{"title":"Stem cell-based therapy for systemic lupus erythematous","authors":"Maryam Zare Moghaddam ,&nbsp;Mohammad Javad Mousavi ,&nbsp;Somayeh Ghotloo","doi":"10.1016/j.jtauto.2024.100241","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100241","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE), an autoimmune disease, is among the most prevalent rheumatic autoimmune disorders. It affects autologous connective tissues caused by the breakdown of self-tolerance mechanisms. During the last two decades, stem cell therapy has been increasingly considered as a therapeutic option in various diseases, including parkinson's disease, alzheimer, stroke, spinal cord injury, multiple sclerosis, inflammatory bowel disease, liver disease, diabete, heart disease, bone disease, renal disease, respiratory diseases, and hematological abnormalities such as anemia. This is due to the unique properties of stem cells that divide and differentiate to the specialized cells in the damaged tissues. Moreover, they impose immunomodulatory properties affecting the diseases caused by immunological abnormalities such as rheumatic autoimmune disorders.</p><p>In the present manuscript, efficacy of stem cell therapy with two main types of stem cells, including mesenchymal stem cell (MSC), and hematopoietic stem cells (HSC) in animal models or human patients of SLE, has been reviewed. Taken together, MSC and HSC therapies improved the disease activity, and severity in kidney, lung, liver, and bone (improvement in the clinical manifestation). In addition, a change in the immunological parameters occurred (improvement in immunological parameters). The level of autoantibodies, including antinuclear antibody (ANA), and anti-double-stranded deoxyribonucleic acid antibodies (dsDNA Abs) reduced. A conversion of Th1/Th2 ratio (in favor of Th2), and Th17/Treg (in favor of Treg) was also detected.</p><p>In spite of many advantages of MSC and HSC transplantations, including efficacy, safety, and increased survival rate of SLE patients, some complications, including recurrence of the disease, occurrence of infections, and secondary autoimmune diseases (SAD) were observed after transplantation that should be addressed in the next studies.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100241"},"PeriodicalIF":3.9,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258990902400011X/pdfft?md5=0d896829d5e6809db86fa1a4317838e3&pid=1-s2.0-S258990902400011X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824266","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":"Changes upon the gluten-free diet of HLA-DQ2 and TRAFD1 gene expression in peripheral blood of celiac disease patients","authors":"Mariavittoria Laezza ,&nbsp;Laura Pisapia ,&nbsp;Benedetta Toro ,&nbsp;Vincenzo Mercadante ,&nbsp;Antonio Rispo ,&nbsp;Carmen Gianfrani ,&nbsp;Giovanna Del Pozzo","doi":"10.1016/j.jtauto.2024.100240","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100240","url":null,"abstract":"<div><h3>Background</h3><p>Celiac disease (CD) is a chronic immuno-mediated enteropathy caused by dietary gluten in genetically susceptible individuals carrying HLA (Human Leukocytes Antigen) genes that encode for DQ2.5 and DQ8 molecules. TRAFD1 (TRAF-type zinc finger domain 1) is a gene recently found associated with CD and defined as a master regulator of IFNγ signalling and of MHC class I antigen processing/presentation. There is no specific drug therapy and the only effective treatment is the gluten-free diet (GFD). The great majority of celiac patients when compliant with GFD have a complete remission of symptoms and recovery of gut mucosa architecture and function. Until now, very few studies have investigated molecular differences occurring in CD patients upon the GFD therapy.</p></div><div><h3>Methods</h3><p>We looked at the expression of both HLA DQ2.5 and TRAFD1 risk genes in adult patients with acute CD at the time of and in treated patients on GFD. Specifically, we measured by qPCR the HLA-DQ2.5 and TRAFD1 mRNAs on peripheral blood mononuclear cells (PBMC) from the two groups of patients.</p></div><div><h3>Results</h3><p>When we compared the HLA-DQ mRNA expression, we didn't find significant variation between the two groups of patients, thus indicating that GFD patients have the same capability to present gliadin antigens to cognate T cells as patients with active disease. Conversely, TRAFD1 was more expressed in PBMC from treated CD subjects. Notably, TRAFD1 transcripts significantly increased in the patients analyzed longitudinally during the GFD, indicating a role in the downregulation of gluten-induced inflammatory pathways.</p></div><div><h3>Conclusion</h3><p>Our study demonstrated that HLA-DQ2.5 and TRAFD1 molecules are two important mediators of anti-gluten immune response and inflammatory process.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100240"},"PeriodicalIF":3.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000108/pdfft?md5=79724f389316f7231ca084c490b40186&pid=1-s2.0-S2589909024000108-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650389","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":"Autoantibodes to GP210 are a metric for UDCA responses in primary biliary cholangitis","authors":"Chan Wang ,&nbsp;Zhuye Qin ,&nbsp;Mingming Zhang ,&nbsp;Yaping Dai ,&nbsp;Luyao Zhang ,&nbsp;Wenyan Tian ,&nbsp;Yuhua Gong ,&nbsp;Sufang Chen ,&nbsp;Can Yang ,&nbsp;Ping Xu ,&nbsp;Xingjuan Shi ,&nbsp;Weifeng Zhao ,&nbsp;Suraj Timilsina ,&nbsp;M. Eric Gershwin ,&nbsp;Weichang Chen ,&nbsp;Fang Qiu ,&nbsp;Xiangdong Liu","doi":"10.1016/j.jtauto.2024.100239","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100239","url":null,"abstract":"<div><h3>Objectives</h3><p>Antibodies to gp210 and sp100 are specific and unique anti-nuclear autoantibodies (ANAs) associated with primary biliary cholangitis (PBC). Importantly the presence of anti-gp210 and anti-sp100 responses is indicative of poor clinical outcomes. However, the utility of measuring titers of these antibodies remains unclear.</p></div><div><h3>Materials and methods</h3><p>Using the in-house purified gp210 (HSA108-C18) and sp100 (amino acid position 296–386), we quantitatively measured serum autoantibodies to gp210 and sp100 using chemiluminescence immunoassay (CLIA) in a very large cohort of 390 patients with PBC, including 259 cases with no prior ursodesoxycholic acid (UDCA) treatment and 131 cases with UDCA treatment. We also analyzed serial changes in anti-gp210 and anti-sp100 levels in 245 sequential samples from 88 patients.</p></div><div><h3>Results</h3><p>In our cross-sectional analysis, we detected anti-gp210 immunoglobulin G (IgG) and anti-sp100 IgG autoantibodies in 129 out of 390 (33.1%) and 80 out of 390 (20.5%) PBC patients, respectively. Multivariate analysis revealed that serum IgG (st.β = 0.35, <em>P</em> = 0.003) and gamma-glutamyltransferase (GGT) (st.β = 0.23, <em>P</em> = 0.042) levels at baseline were independently associated with anti-gp210 concentrations. In serial testing, we observed significant fluctuations in anti-gp210 antibody levels. These fluctuations reflected responsiveness to UDCA therapy, particularly in anti-gp210-positive patients with initially lower concentrations in the stages of disease.</p></div><div><h3>Conclusions</h3><p>Our study reflects that quantitative changes of anti-gp210 antibody are indicative of UDCA responses. There is a great need for newer metrics in PBC and we suggest that a more detailed and longer study of these unique ANAs is warranted.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100239"},"PeriodicalIF":3.9,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000091/pdfft?md5=122fa1d258d4e30ca9277942c974682d&pid=1-s2.0-S2589909024000091-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140191712","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":"Treatment of non-systemic Sjögren's syndrome: Potential prevention of systematization with immunosuppressant agent/biotherapy","authors":"Aude Belbézier ,&nbsp;Thi Thu Thuy Nguyen ,&nbsp;Mélanie Arnaud ,&nbsp;Bruna Ducotterd ,&nbsp;Marie Vangout ,&nbsp;Alban Deroux ,&nbsp;Catherine Mansard ,&nbsp;Françoise Sarrot-Reynauld ,&nbsp;Laurence Bouillet","doi":"10.1016/j.jtauto.2024.100238","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100238","url":null,"abstract":"<div><h3>Background</h3><p>Sjögren's syndrome (SS) is a systemic autoimmune pathology manifested mainly by a dry syndrome, intense asthenia and arthromyalgia. Systemic manifestations may also occur. Since 2019, immunosuppressant agents (IS) or biotherapies are recommended only for patients with systemic involvement. However, before 2019, in some cases, paucisymptomatic patients had been treated with IS/biotherapies, often off-label. <strong>Objective</strong>: We propose to evaluate the benefit and safety of using IS/biotherapy in patients with SS without systemic involvement. <strong>Methods:</strong> We retrospectively collected the clinical records of all patients with SS diagnosed according to ACR/EULAR diagnostic criteria followed up between January 1980 and October 2023 at Grenoble University Hospital (France). <strong>Results:</strong> Eighty-three patients were included: 64 with an initially non-systemic form. Of these patients with an initially non-systemic form, 24 were treated with IS/biotherapy. None of them developed secondary systematization, whereas 11 out of 40 patients in the untreated group did (p &lt; 0.05). On the other hand, IS/biotherapy did not appear to improve dry syndrome. There were no serious adverse events. <strong>Conclusion:</strong> Early introduction of an IS/biotherapy treatment appears to provide a benefit for the patient without side effects.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100238"},"PeriodicalIF":3.9,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S258990902400008X/pdfft?md5=2941ee00a1b6c48966a06947f00da1c8&pid=1-s2.0-S258990902400008X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140069353","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":"Autoimmunity in centenarians. A paradox","authors":"Juan-Manuel Anaya ,&nbsp;Ivan David Lozada-Martinez ,&nbsp;Isaura Torres ,&nbsp;Yehuda Shoenfeld","doi":"10.1016/j.jtauto.2024.100237","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100237","url":null,"abstract":"<div><p>Autoimmune diseases (ADs) are one of the groups of chronic illnesses that impose a significant burden of disease and health costs worldwide. Age is a crucial risk factor for the onset of ADs. Theoretically, it is inferred that with organic and immune system aging, the loss of immune tolerance and specificity of immune activity becomes more intense, the probability of autoimmunity is increasing. However, there is a group of individuals whose prevalence of ADs is very low or non-existent, despite the biological aging. This paradox in autoimmunity raises questions. Centenarians, individuals who are over 100 years old, are possibly the most successful model of biological aging in humans. Most of these individuals exhibit a favorable health phenotype. To date, primary data evidence and potential hypotheses explaining this phenomenon are lacking globally, even though this paradox could provide valuable, original, and relevant information regarding the understanding of risk or protective factors, biological drivers, and biomarkers related to autoimmunity. Herein we discuss some hypothesis that may explain the absence of ADs in centenarians, including inflammaging, immunosenescence and immune resilience, immune system hyperstimulation, proteodynamics, and genetics.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100237"},"PeriodicalIF":3.9,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000078/pdfft?md5=d73ac460af023a75956b96beaf06a48e&pid=1-s2.0-S2589909024000078-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030332","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 effects of omega-3 fatty acids supplementation on hemoglobin, hematocrit, and platelet levels of patients with ESRD condition undergoing dialysis","authors":"Zahra Mahmoudi ,&nbsp;Zahra Roumi ,&nbsp;Seyed Ali Askarpour ,&nbsp;Zahra Mousavi ,&nbsp;Hanieh Shafaei ,&nbsp;Neda Valisoltani ,&nbsp;Mahsa Shapouri ,&nbsp;Seyed Reza Mirshafaei ,&nbsp;Pouya Mirzaee ,&nbsp;Khadijeh Abbasi Mobarakeh ,&nbsp;Elahe Taghavi Sufiani ,&nbsp;Zeinab Motiee Bijarpasi ,&nbsp;Zeynab Motiei ,&nbsp;Masoud Khosravi ,&nbsp;Saeid Doaei ,&nbsp;Maryam Gholamalizadeh","doi":"10.1016/j.jtauto.2024.100233","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100233","url":null,"abstract":"<div><h3>Background</h3><p>Concomitant inflammation may boost the cardiovascular complications in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). Omega-3 fatty acids may have certain health benefits in HD patients. The aim of this study was to investigate the effects of omega-3 fatty acids supplementation on hematocrit (HCT), hemoglobin (HB) level and platelet (PLT) counts of HD patients.</p></div><div><h3>Methods</h3><p>A randomized controlled trial was conducted on HD patients at a private dialysis center in Rasht, Iran. Three omega-3 fatty acid supplement capsules (3 g/d) were administered daily for two months to patients in the intervention group (n = 55). The control group (n = 60) were given three placebo capsules containing medium chain triglyceride (MCT) oil, similar to the supplemental dose of the intervention group at the same period. Three parameters of HCT, HB and PLT were measured at baseline and after the intervention.</p></div><div><h3>Results</h3><p>The PLT count decreased in the intervention group compared to the control group (173.38 ± 74.76 vs. 227.68 ± 86.58 10³/mm³, F = 4.83, P = 0.03). No significant change was found on the levels of HCT and HB parameters between the two groups after the intervention.</p></div><div><h3>Conclusion</h3><p>Omega-3 supplementation in HD patients may decrease the risk of forming blood clots in the blood vessels. Further studies are warranted.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100233"},"PeriodicalIF":3.9,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000030/pdfft?md5=5bcba8760b794c6c65baed779d81fc5c&pid=1-s2.0-S2589909024000030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140030333","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":"Presentation and progression of MPO-ANCA interstitial lung disease","authors":"Lorenzo Salvati ,&nbsp;Boaz Palterer ,&nbsp;Elena Lazzeri ,&nbsp;Emanuele Vivarelli ,&nbsp;Marina Amendola ,&nbsp;Marco Allinovi ,&nbsp;Leonardo Caroti ,&nbsp;Alessio Mazzoni ,&nbsp;Laura Lasagni ,&nbsp;Giacomo Emmi ,&nbsp;Edoardo Cavigli ,&nbsp;Marco Del Carria ,&nbsp;Linda Di Pietro ,&nbsp;Mariangela Scavone ,&nbsp;Daniele Cammelli ,&nbsp;Federico Lavorini ,&nbsp;Sara Tomassetti ,&nbsp;Elisabetta Rosi ,&nbsp;Paola Parronchi","doi":"10.1016/j.jtauto.2024.100235","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100235","url":null,"abstract":"<div><p>The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100235"},"PeriodicalIF":3.9,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000054/pdfft?md5=9a7374416762e09d66959b84f16dd0ea&pid=1-s2.0-S2589909024000054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992559","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":"Sarcoidosis and lymphoma mortality risk: An observational study from the Spanish National Registry","authors":"Víctor Moreno-Torres ,&nbsp;María Martínez-Urbistondo ,&nbsp;Pedro Durán-del Campo ,&nbsp;Pablo Tutor ,&nbsp;Begoña Rodríguez ,&nbsp;Raquel Castejón ,&nbsp;Susana Mellor-Pita","doi":"10.1016/j.jtauto.2024.100236","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100236","url":null,"abstract":"<div><h3>Introduction</h3><p>Patients with sarcoidosis have a lower survival rate than the general population, in part due to cardiovascular disease, infections and neoplasms. Our objective was to evaluate the impact of haematological neoplasms (HN) and lymphomas on sarcoidosis patient mortality in a nation-wide analysis conducted in Spain, a country with a population of 47 million.</p></div><div><h3>Methods</h3><p>Retrospective and observational comparison of the HN related deaths in sarcoidosis patients and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of sarcoidosis on the risk of dying from each HN lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed.</p></div><div><h3>Results</h3><p>In the period 2016 and 2019, 139,531 in-hospital deaths from neoplasms were certified in Spain (77 in patients with sarcoidosis). Patients with sarcoidosis died at younger age than the general Spanish population (72.9 vs 77.6, p&lt;0.001). Sarcoidosis patients presented a higher mortality risk from HN (20.8% vs 8.9%, p=0.001, OR=2.64, 95% CI 1.52-4.59), attributable to the higher proportion of deaths from non-Hodgkin lymphoma (NHL), (9.2% vs 2.9%, p=0.006, OR= 3.33, 95% CI 1.53-7.25) from both B cell (6.6% vs 2.5%, p=0.044, OR= 2.62, 95% 1.06-6.5) and T/NK cell lineages (2.6% vs 0.3%, p=0.024, OR= 7.88, 95% CI 1.92-32.29) as well as HN with uncertain behavior and myeloproliferative disorders (2.6% vs 0.3%, p=0.018, OR= 11.88, 95% CI 2.88-49.02). The mean age of sarcoidosis patients who died from HN (63.6 vs 71.9, p=0.032) and non-Hodgkin lymphoma (56.9 vs 71, p=0.009) was lower than that of the general population</p></div><div><h3>Conclusion</h3><p>Patients with sarcoidosis present a higher risk of premature death from HN, including NHL from B, T/NK cell lineage and myeloproliferative disorders in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early-detection programs for these conditions should be investigated and considered carefully.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100236"},"PeriodicalIF":3.9,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000066/pdfft?md5=aee45af346db935182d22e523806b9a0&pid=1-s2.0-S2589909024000066-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139935800","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 CCR6 functional polymorphisms with Primary Biliary Cholangitis","authors":"Mingming Zhang ,&nbsp;Zhuye Qin ,&nbsp;Yexi Huang ,&nbsp;Wenyan Tian ,&nbsp;You Li ,&nbsp;Chan Wang ,&nbsp;Weifeng Zhao ,&nbsp;Yaping Dai ,&nbsp;Xingjuan Shi ,&nbsp;M. Eric Gershwin ,&nbsp;Xiong Ma ,&nbsp;Meilin Wang ,&nbsp;Xiangdong Liu ,&nbsp;Weichang Chen ,&nbsp;Fang Qiu","doi":"10.1016/j.jtauto.2024.100234","DOIUrl":"10.1016/j.jtauto.2024.100234","url":null,"abstract":"<div><p>The biliary epithelial cells release CC chemokine receptor 6 (<em>CCR6</em>) ligand 20 (<em>CCL20</em>), leading to recruitment of CCR6⁺ T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. Previous genome-wide multi-national meta-analysis, including our Han Chinese cohort, showed significant association of <em>CCR6</em> and <em>CCL20</em> single nucleotide polymorphisms (SNP) with PBC. We report here that significantly associated SNPs, identified in the <em>CCR6</em> locus based on our Han Chinese genome-wide association study, can be separated into “protective” and “risk” groups, but only “risk” SNPs were confirmed using a separate Han Chinese PBC cohort. Only weak association of <em>CCL20</em> SNPs was observed in Han Chinese PBC cohorts. Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased <em>CCR6</em> expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort.</p></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100234"},"PeriodicalIF":3.9,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000042/pdfft?md5=bde0fac6bd5f49d1477123acbe1d46a0&pid=1-s2.0-S2589909024000042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139824762","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":"Evaluating the inhibition of IL-17A and TNFα in a cartilage explant model cultured with Th17-derived cytokines","authors":"Solveig Skovlund Groen ,&nbsp;Anne-Christine Bay-Jensen ,&nbsp;Christian S. Thudium ,&nbsp;Morten H. Dziegiel ,&nbsp;Marie Skougaard ,&nbsp;Simon Francis Thomsen ,&nbsp;Signe Holm Nielsen","doi":"10.1016/j.jtauto.2024.100231","DOIUrl":"https://doi.org/10.1016/j.jtauto.2024.100231","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;T-helper 17 (Th17) cells produce IL-17A playing a critical role in activating the pathogenic chain leading to joint tissue inflammation and destruction. Elevated levels of Th17 cells and IL-17A have been detected in skin lesions, blood, and synovial fluid from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Moreover, IL-17A inhibitors suppress disease activity in psoriasis, PsA and AS, supporting the evidence of IL-17A contributing to the disease pathogenesis. Although, IL-17A inhibitors are widely approved, it remains unclear how the inhibitory effect of IL-17A alters the extracellular matrix (ECM) of the joint in a Th17-conditioned inflammatory milieu. Therefore, the aim of this study was to establish a cartilage model cultured with conditioned medium from Th17 cells and inhibitors to explore the effect of IL-17A inhibition on joint tissue remodeling.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Naïve CD4&lt;sup&gt;+&lt;/sup&gt; T cells from healthy human buffy coat were differentiated into Th17 cells, followed by Th17 cell activation to secrete Th17-related cytokines and molecules into media. The activated Th17 cells were isolated from the conditioned media (CM) and analyzed using flow cytometry to verify Th17 cell differentiation. The CM were assessed with ELISA to quantify the concentrations of cytokines secreted into the media by the Th17 cells. Healthy bovine cartilage explants were cultured with the Th17-CM and treated with IL-17A and TNFα inhibitors for 21 days. In harvested supernatant from the cartilage cultures, MMP- and ADAMTS-mediated biomarker fragments of type II collagen, aggrecan, and fibronectin were measured by ELISA to investigate the ECM remodeling within the cartilage tissue.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Th17-CM stimulated a catabolic response in the cartilage. Markers of type II collagen and aggrecan degradation were upregulated, while anabolic marker of type II collagen formation remained on similar levels as the untreated explants. The addition of IL-17A inhibitor to Th17-CM decreased the elevated type II collagen and aggrecan degradation, however, degenerative levels were still elevated compared to untreated group. The addition of TNFα inhibitor completely reduced both type II collagen and aggrecan degradation compared to untreated explants. Moreover, the TNFα inhibitor treatment did not alter the type II collagen formation compared to untreated group.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;This study suggests that inhibition of IL-17A in Th17-conditioned cartilage tissue only partially reduced the MMP-mediated type II collagen degradation and ADAMTS-mediated aggrecan degradation, while the TNFα inhibitor treatment fully reduced both MMP- and ADAMTS-mediated ECM degradation. This exploratory study where ECM biomarkers are combined with Th17-conditioned &lt;em&gt;ex vivo&lt;/em&gt; model may hold great potential as output for describing joint disease mechanisms and predicting structural effects of trea","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"8 ","pages":"Article 100231"},"PeriodicalIF":3.9,"publicationDate":"2024-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589909024000017/pdfft?md5=61ffc6f0ec57f666cac3c55f9b5c7838&pid=1-s2.0-S2589909024000017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139436568","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}