Journal of Translational Autoimmunity最新文献

{"title":"Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients","authors":"Rick Wilbrink ,&nbsp;Stefan F.H. Neys ,&nbsp;Rudi W. Hendriks ,&nbsp;Anneke Spoorenberg ,&nbsp;Frans G.M. Kroese ,&nbsp;Odilia B.J. Corneth ,&nbsp;Gwenny M.P.J. Verstappen","doi":"10.1016/j.jtauto.2025.100270","DOIUrl":"10.1016/j.jtauto.2025.100270","url":null,"abstract":"<div><h3>Objective</h3><div>Radiographic axial spondyloarthritis (r-axSpA) is a chronic rheumatic disease in which innate immune cells and T cells are thought to play a major role. However, recent studies also hint at B cell involvement. Here, we performed an in-depth analysis on alterations within the B-cell compartment from r-axSpA patients.</div></div><div><h3>Methods</h3><div>We performed immune gene expression profiling on total peripheral blood B cells from 8 r-axSpA patients and 8 healthy controls (HCs). Next, we explored B cell subset distribution and B-cell receptor (BCR) signaling responses in circulating B cells from 28 r-axSpA patients and 15 HCs, by measuring spleen tyrosine kinase, phosphoinositide 3-kinase and extracellular signal regulated kinase 1/2 phosphorylation upon α-Ig stimulation using phosphoflow cytometry.</div></div><div><h3>Results</h3><div>Immune gene expression profiling indicated an elevated pathway score for BCR signaling in total B cells from r-axSpA patients compared with HCs. Flow cytometric analysis revealed an increase in frequency of both total and double-negative 2 (DN2) B cells in r-axSpA patients compared with HCs. In r-axSpA patients, DN2 B cells displayed an isotype shift towards IgA. Remarkably, where DN2 B cells from HCs were hyporesponsive, these cells displayed significant proximal BCR signaling responses in r-axSpA patients. Enhanced BCR signaling responses were also observed in the transitional and naïve B cell population from r-axSpA patients compared with HCs. The enhanced BCR signaling responses in DN2 B cells correlated with clinical disease parameters.</div></div><div><h3>Conclusion</h3><div>In r-axSpA patients, circulating DN2 B cells are expanded and, together with transitional and naïve B cells, display significantly enhanced BCR signaling responses upon stimulation. Together, our data suggest B cell involvement in the pathogenesis of r-axSpA.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100270"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143175347","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":"Tofacitinib downregulates JAK1 and JAK3 on human intestinal monocytes and macrophages without affecting dendritic cells phenotype or function","authors":"Elisa Arribas-Rodríguez ,&nbsp;Ángel De Prado ,&nbsp;Beatriz de Andrés ,&nbsp;Benito Velayos ,&nbsp;Jesús Barrio ,&nbsp;Alejandro Romero ,&nbsp;Francisco Javier García-Alonso ,&nbsp;Álvaro Martín-Muñoz ,&nbsp;José A. Garrote ,&nbsp;Eduardo Arranz ,&nbsp;Luis Fernández-Salazar ,&nbsp;David Bernardo","doi":"10.1016/j.jtauto.2025.100271","DOIUrl":"10.1016/j.jtauto.2025.100271","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is an inflammatory disorder of the gastrointestinal tract. Although Tofacitinib, which inhibits the JAK1 and JAK3 signalling pathway, is approved to treat patients with UC, its specific mechanism of action remain elusive. Given the central role that conventional dendritic cells (cDC) elicit in gut homeostasis, we hypothesised that Tofacitinib acts modulating cDC function in UC.</div></div><div><h3>Methods</h3><div>Human biopsies were obtained from colon of controls, and patients with UC (active and quiescent). Lamina propria mononuclear cells (LPMC) were <em>ex-vivo</em> cultured in the presence/absence of Tofacitinib. The specific effect elicited over human intestinal cDC, monocytes and macrophages was assessed by flow cytometry. cDC were also enriched following Tofacitinib conditioning in order to assess its effect over naïve T-cells.</div></div><div><h3>Results</h3><div>Several human intestinal cDC, monocyte and macrophage subsets can be found in the human colon, with these cells being more similar between controls and patients with qUC referred to patients with aUC. Following <em>ex-vivo</em> culture, Tofacitinib downregulated JAK1 expression on intestinal monocytes from patients with both active and quiescent UC. As for macrophages, JAK1 was decreased on patients with active UC while JAK was downregulated on macrophages from patients with quiescent disease. Tofacitinib did not modulate the phenotype or function of human intestinal cDC.</div></div><div><h3>Conclussion</h3><div>Tofacitinib does not modulate the phenotype and function of human intestinal cDC in UC. On the contrary, it displays a differential capacity to modulate intestinal monocyte and macrophage phenotype. Future studies should address whether it also translates into a differential function of these cells.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100271"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143176736","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 added value of coupling anti-dsDNA and anti-chromatin antibodies in follow-up monitoring of systemic lupus erythematosus patients","authors":"Caroline Carlé ,&nbsp;Françoise Fortenfant ,&nbsp;Chloé Bost ,&nbsp;Julie Belliere ,&nbsp;Stanislas Faguer ,&nbsp;Dominique Chauveau ,&nbsp;Antoine Huart ,&nbsp;David Ribes ,&nbsp;Laurent Alric ,&nbsp;Gregory Pugnet ,&nbsp;Laurent Sailler ,&nbsp;Yves Renaudineau","doi":"10.1016/j.jtauto.2025.100274","DOIUrl":"10.1016/j.jtauto.2025.100274","url":null,"abstract":"<div><h3>Objective</h3><div>The autoimmune response to chromatin (Chr) or one of the nucleosome components (double stranded (ds)DNA and histones) is typically associated with the development of systemic lupus erythematosus (SLE). Related autoantibodies (Ab) are heterogeneous and, among them, anti-dsDNA Ab are part of the classification criteria and recommended for monitoring SLE with regards to lupus flares and therapy responses. However, anti-dsDNA Ab biomarker performances are weak; therefore, coupling anti-dsDNA with anti-Chr Ab can be proposed, which is the aim of this study.</div></div><div><h3>Methods</h3><div>In this single center study from 2009 to 2024, 269 SLE patients with follow-up information were retrospectively selected from a population of 646 individuals, including 325 SLE patients, who tested positive for anti-dsDNA and/or anti-Chr Ab (Bioplex 2200™). Bio-clinical information during follow-up were assessed at several time points through medical records in order to explore associations between the anti-dsDNA/Chr Ab profile with disease presentation, and anti-dsDNA/Chr Ab fluctuations with disease activity using clinical SLEDAI-2K, flares requiring specific treatment, and the therapeutic response.</div></div><div><h3>Results</h3><div>At inclusion in the follow-up analysis, corresponding to diagnosis (116/269, 43.1 %) or flare (153/269, 56.9 %), SLE patients were subdivided into three serological groups: the double positive dsDNA/Chr group (DP+, 190/269: 70.6 %), followed by the single positive Chr group (SP-C+, 42/269: 15.6 %), and the single positive dsDNA group (SP-D+, 37/269: 13.8 %). The DP + group, which presented important anti-dsDNA/Ab variations during follow-up, was at risk to develop lupus nephritis (56.8 % versus 2.4 % in SP-C+ and 29.7 % in SP-D+ groups, p &lt; 0.04) and serositis (30 % versus 9.5 % in SP-C+ group, <em>p</em> = 0.006). During follow-up, anti-dsDNA and Chr Ab levels in the SP-C+ and SP-D+ groups remained stable over time irrespective of disease activity, flares, and therapeutic response. Regarding the DP + group, disease activity was correlated with both anti-dsDNA (RmCorr = 0.46, p = 1.6x110-⁹¹) and anti-Chr (RmCorr = 0.38, p = 2.8x10-⁶⁰) Ab levels, which can be used to predict flares. Following therapy introduction, Ab reduction occurred in all patients from the DP + group with a more pronounced effect reported in complete responders.</div></div><div><h3>Conclusion</h3><div>coupling anti-dsDNA with anti-Chr Ab detection at disease initiation/flare allows definition of endotypes, which is useful to follow disease activity, predict lupus nephritis/serositis, and anticipate therapeutic response in the DP + group.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100274"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143175372","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":"Autoantibodies in systemic sclerosis: From disease bystanders to pathogenic players","authors":"Aurélien Chepy ,&nbsp;Aurore Collet ,&nbsp;David Launay ,&nbsp;Sylvain Dubucquoi ,&nbsp;Vincent Sobanski","doi":"10.1016/j.jtauto.2025.100272","DOIUrl":"10.1016/j.jtauto.2025.100272","url":null,"abstract":"<div><div>Autoantibodies (Aab) are recognized as key indicators in the diagnosis, classification, and monitoring of systemic autoimmune diseases (AID). Recent studies have expanded knowledge through the discovery of new antigenic targets, advanced methods for measuring Aab levels, and understanding their possible pathogenic roles in AID. This narrative review uses systemic sclerosis (SSc) as an example to highlight the importance of Aab associated with HEp-2 immunofluorescence assay positivity (traditionally referred as antinuclear antibodies [ANA]), exploring recent developments in the field. Firstly, we outline the various types of ANA found in SSc and their links with specific disease features. Newly discovered antibodies shed light on SSc cases where Aab had previously gone unidentified. Secondly, we emphasize the necessity for novel quantitative techniques to track Aab levels over time by gathering data regarding the timing of Aab occurrence relative to SSc symptoms and the relationships between Aab concentrations and disease severity. Finally, we discuss the experimental findings suggesting a potential direct role of Aab in the development of SSc. The advancements surrounding Aab provide insights into new disease mechanisms and may lead to innovative diagnostic and treatment approaches.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100272"},"PeriodicalIF":4.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174952","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":"Monitoring the follow-up of autoimmune chronic atrophic gastritis using parietal cell antibodies and markers of gastric function","authors":"Maria Piera Panozzo ,&nbsp;Antonio Antico ,&nbsp;Nicola Bizzaro","doi":"10.1016/j.jtauto.2025.100273","DOIUrl":"10.1016/j.jtauto.2025.100273","url":null,"abstract":"<div><div>Increased interest in the pathogenesis and the evolution of autoimmune chronic atrophic gastritis (A-CAG) has led to the search for serological markers that can be used to detect changes in the gastric mucosa at an early stage and to monitor the course of the disease. Parietal cell autoantibodies have been proposed as suitable immunological markers of atrophic damage, as they can be detected in the serum when symptoms of gastritis are not yet present. However, the utility of measuring only the level of parietal cell autoantibodies in the follow-up of A-CAG does not appear to suffice. Recent evidence has suggested that, in monitoring A-CAG, parietal cell antibodies should be associated with an evaluation of gastric function through biochemical and hormonal tests, such as pepsinogens and gastrin 17. This integrated approach will allow for the more effective real-time monitoring of the state of the gastric mucosa. As A-CAG is a progressive disorder associated with an increased risk of gastric cancer and neuroendocrine tumors, the precise follow-up of patients with gastric atrophy needs to be better defined. Further longitudinal studies in large cohorts must be performed with long-term follow-up.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100273"},"PeriodicalIF":4.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Across ancestries, HLA-B∗08:01∼DRB1∗03:01 (DR3) and HLA-DQA∗01:02 (DR2) increase the risk to develop juvenile-onset systemic lupus erythematosus through low complement C4 levels","authors":"Yves Renaudineau ,&nbsp;Amandine Charras ,&nbsp;Valentina Natoli ,&nbsp;Nicolas Congy-Jolivet ,&nbsp;Sam Haldenby ,&nbsp;Xuan Liu ,&nbsp;Yongxiang Fang ,&nbsp;Eve MD. Smith ,&nbsp;Michael W. Beresford ,&nbsp;Christian M. Hedrich","doi":"10.1016/j.jtauto.2025.100268","DOIUrl":"10.1016/j.jtauto.2025.100268","url":null,"abstract":"<div><h3>Objective</h3><div>Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease with a strong genetic component. Genetic burden is higher in children when compared to patients with adult-onset SLE, contributing to earlier disease expression and more severe phenotypes. The human leukocyte antigen (HLA) cluster on chromosome 6p21.3 is among the most variable genomic regions, representing a major risk-factor for SLE in adults. Its impact on juvenile-onset (j)SLE remains largely unstudied.</div></div><div><h3>Methods</h3><div>High-resolution sequencing of HLA class I (A, B, C), class II (DRB1, DQA1, DQB1) and class III (complement <em>C2</em>) was undertaken in the multi-ancestral UK JSLE Cohort including participants of Caucasian (n = 151, 48.8 %), Asian (n = 108, 35.0 %) and African/Caribbean (n = 50, 16.2 %) descent. Considering ancestral variation, clinical associations were tested at the level of alleles (2-field resolution), associated HLA protein sequences (antigen binding domains, 4-field resolution), and extended haplotypes (DRh).</div></div><div><h3>Results</h3><div>Although important ancestral recombination was reported for HLA-DR2 and -DR3 haplotypes, risk associated with jSLE was conserved at related alleles (DR2h: DRB1∗15:01, DQA∗01:02, DQB1∗06:02; DR3h: C∗07:02 [Asian], B∗08:01, <em>C2</em> rs9332730 [Asian], DRB1∗03:01). HLA-DR7 haplotypes (DRB1∗07:01, OR = 0.44, 95 % CI:0.27–0.72, p = 0.0004; DQA1∗02:01, OR = 0.34, 95 % CI:0.21–0.56, p = 1.8 × 10⁻⁶) protect Asians from jSLE development. Among 23 clinical variables recorded, the main association was found between low levels of complement C4 in Caucasian carriers of HLA-DR3h. This was not the case in Asians due to recombination with HLA-C∗07:02 and integration of the <em>C2</em> rs9332730 minor allele. Low C4 serum levels associated with HLA-DQA1∗01:02 (DR2h) in Caucasians after excluding HLA-DR3h carriers from the analysis. An association between low white blood cell counts and HLA-A∗03:01P was observed across ancestries.</div></div><div><h3>Conclusion</h3><div>Genetic variation in the <em>HLA</em> cluster associates with organ domain involvement (hematological) and complement levels in jSLE. Lupus-associated <em>HLA</em> haplotypes vary between ancestral groups, underscoring the importance of multi-ancestral approaches to genetic studies in SLE and other autoimmune/inflammatory diseases.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100268"},"PeriodicalIF":4.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases","authors":"Michaela Fehringer,&nbsp;Thomas Vogl","doi":"10.1016/j.jtauto.2025.100269","DOIUrl":"10.1016/j.jtauto.2025.100269","url":null,"abstract":"<div><div>Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes). This similarity can lead to cross-reactive antibodies and T-cell receptors, resulting in an immune response against autoantigens. Both commensal microbes in the human microbiome and pathogens can trigger molecular mimicry, thereby potentially contributing to the onset of ARDs.</div><div>In this review, we focus on the role of molecular mimicry in the onset of rheumatoid arthritis and systemic lupus erythematosus. Moreover, implications of molecular mimicry are also briefly discussed for ankylosing spondylitis, systemic sclerosis and myositis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100269"},"PeriodicalIF":4.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large soluble CD18 complexes with exclusive ICAM-1-binding properties are shed during immune cell migration in inflammation","authors":"Alexey Ferapontov ,&nbsp;Anders Mellemkjær ,&nbsp;Helen M. McGettrick ,&nbsp;Thomas Vorup-Jensen ,&nbsp;Tue W. Kragstrup ,&nbsp;Kristian Juul-Madsen","doi":"10.1016/j.jtauto.2025.100266","DOIUrl":"10.1016/j.jtauto.2025.100266","url":null,"abstract":"<div><div>The family of heterodimeric CD11/CD18 integrins facilitate leukocyte adhesion and migration in a wide range of normal physiologic responses, as well as in the pathology of inflammatory diseases. Soluble CD18 (sCD18) is found mainly in complexes with hydrodynamic radii of 5 and 7.2 nm, suggesting a compositional difference. Earlier work reported that the complexes include at least part of the CD11a or CD11b chains containing the intercellular adhesion molecule (ICAM)-1 binding domain, and that sCD18 is capable of quantitatively competing with the cell membrane-bound form for ICAM-1 binding. However, it is not clear if the size differences between the sCD18 complexes reflect any functional variance regarding shedding from the cell membrane or binding to ICAM-1. Here, we show evidence that sCD18 found in serum regulates release of the proinflammatory cytokine monocyte chemoattractant protein-1 (MCP-1/CCL2) from fibroblast-like synovial cells. Further, only large sCD18 complexes are capable of binding to ICAM-1. Migrating neutrophils shed large, but not small, sCD18 complexes. Together, these observations explain results measured from patients with rheumatoid arthritis (RA), where large sCD18 complexes dominated in local inflammatory processes involving neutrophil influx into zones of inflammation. Our data points to a previously unappreciated aspect of sCD18 integrin biology as regulators of inflammation in the context of migrating leukocyte. Surprisingly, this regulation is tied to sCD18 complex size, opening new opportunities for therapeutic intervention in serious inflammatory diseases such as arthritis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100266"},"PeriodicalIF":4.7,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047987","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":"Iron metabolism in rheumatic diseases","authors":"Aliakbar Givian ,&nbsp;Amin Azizan ,&nbsp;Ahmadreza Jamshidi ,&nbsp;Mahdi Mahmoudi ,&nbsp;Elham Farhadi","doi":"10.1016/j.jtauto.2025.100267","DOIUrl":"10.1016/j.jtauto.2025.100267","url":null,"abstract":"<div><div>Iron is a crucial element for living organism in terms of oxygen transport, hematopoiesis, enzymatic activity, mitochondrial respiratory chain function and also immune system function. The human being has evolved a mechanism to regulate body iron. In some rheumatic diseases such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), and gout, this balanced iron regulation is impaired. Altered iron homeostasis can contribute to disease progression through ROS production, fibrosis, inflammation, abnormal bone homeostasis, NETosis and cell senescence. In this review, we have focused on the iron metabolism in rheumatic disease and its role in disease progression.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100267"},"PeriodicalIF":4.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047986","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 role of UV-induced cutaneous matrix metalloproteinases and mi-RNAs in the pathogenesis of lupus erythematosus","authors":"I. Ivanova,&nbsp;T. Svilenska,&nbsp;T. Maisch,&nbsp;S. Karrer,&nbsp;D. Niebel,&nbsp;M. Berneburg,&nbsp;B. Kurz","doi":"10.1016/j.jtauto.2024.100265","DOIUrl":"10.1016/j.jtauto.2024.100265","url":null,"abstract":"<div><div>Cutaneous (CLE) and systemic lupus erythematosus (SLE) are autoimmune diseases with a multifactorial pathogenesis. Ultraviolet radiation (UVR) is the most important trigger of CLE; however, the degree of photosensitivity varies between the clinical subtypes. The expression of matrix metalloproteinases (MMPs)—important enzymes involved in skin turnover and homeostasis—is modulated by UVR.</div><div>To investigate the causality of the clinically observed effects of UVR, sun-exposed lesional skin samples from patients with different subtypes of lupus erythematosus (LE) were examined by immunohistochemistry for the expression of MMP1 and MMP28 and compared with biopsies from polymorphous light eruption (PLE) and healthy skin (HS). The expression of micro-RNAs (miR-31 and miR-150)—regulators of MMP expression and cellular metabolism—in the samples was determined by in-situ hybridization and correlated with the expression of the glucose transporter 1 (GLUT1) receptor to examine potential metabolic regulation. To assess potential UVR regulation of MMP28, we performed <em>in vitro</em> experiments in healthy keratinocytes and fibroblasts.</div><div>MMP28 expression was differentially affected by UVA1 and UVB irradiation in keratinocytes and fibroblasts. Compared with all other LE subtypes, as well as PLE and HS samples, MMP28 expression in Chilblain LE skin showed a distinct vertical distribution, reaching as far as the upper layers of the dermis. This vertical expression pattern coincided with decreased GLUT1 levels and with increased expression of miR-31 and miR-150 in the epidermis of patients with Chilblain LE. These data provide evidence for a potential metabolic dysregulation that may play a role in the etiology of LE. Furthermore, our results suggest MMP28 as a novel complementary marker in Chilblain LE diagnosis.</div></div>","PeriodicalId":36425,"journal":{"name":"Journal of Translational Autoimmunity","volume":"10 ","pages":"Article 100265"},"PeriodicalIF":4.7,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143013303","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}