{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T19:42:39Z","timestamp":1794426159765,"version":"4.9.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is a distinctive serology hallmark of dermatomyositis (DM). As an autoantigen, MDA5 is a cytoplasmic RNA recognition receptor. The aim of this study was to address the question of whether the RNA-containing immune complex (IC) formed by MDA5 and anti-MDA5 could activate type I interferon (IFN) response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      Patients with anti-MDA5\n                      <jats:sup>+<\/jats:sup>\n                      DM (\n                      <jats:italic>n<\/jats:italic>\n                      = 217), anti-MDA5\n                      <jats:sup>\u2212<\/jats:sup>\n                      DM (\n                      <jats:italic>n<\/jats:italic>\n                      = 68), anti-synthase syndrome (ASyS,\n                      <jats:italic>n<\/jats:italic>\n                      = 57), systemic lupus erythematosus (SLE,\n                      <jats:italic>n<\/jats:italic>\n                      = 245), rheumatoid arthritis (RA,\n                      <jats:italic>n<\/jats:italic>\n                      = 89), and systemic sclerosis (SSc,\n                      <jats:italic>n<\/jats:italic>\n                      = 30) and healthy donors (HD,\n                      <jats:italic>n<\/jats:italic>\n                      = 94) were enrolled in our studies. Anti-MDA5 antibody was detected by line blotting, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, and Western blotting. Cytokine profiling was determined by multiplex flow cytometry, and IFN-\u03b1 was further measured by ELISA. Type I IFN-inducible genes were detected by quantitative PCR (qPCR). RNA\u2013IC binding was analyzed by RNA immunoprecipitation. Plasmacytoid dendritic cells (pDCs) derived from healthy donors were cultivated and stimulated with MDA5 ICs with or without RNase and Toll-like receptor 7 (TLR-7) agonist. The interaction between MDA5 ICs and TLR7 was evaluated by immunoprecipitation and confocal microscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      According to our in-house ELISA, the presence of anti-MDA5 antibody in 76.1% of DM patients, along with 14.3% of SLE patients who had a lower titer yet positive anti-MDA5 antibody, was related to the high level of peripheral IFN-\u03b1. ICs formed by MDA5 and anti-MDA5 were potent inducers of IFN-\u03b1\n                      <jats:italic>via<\/jats:italic>\n                      TLR-7 in an RNA-dependent manner\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data provided evidence of the mechanistic relevance between the anti-MDA5 antibody and type I IFN pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2021.743704","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T21:29:34Z","timestamp":1634333374000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["RNA-Containing Immune Complexes Formed by Anti-Melanoma Differentiation Associated Gene 5 Autoantibody Are Potent Inducers of IFN-\u03b1"],"prefix":"10.3389","volume":"12","author":[{"given":"Kaiwen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfeng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanlong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakai","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24621","article-title":"RNA Helicase Encoded by Melanoma Differentiation-Associated Gene 5 Is a Major Autoantigen in Patients With Clinically Amyopathic Dermatomyositis: Association With Rapidly Progressive Interstitial Lung Disease","volume":"60","author":"Sato","year":"2009","journal-title":"Arthritis Rheum"},{"key":"B2","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s12016-020-08822-5","article-title":"Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis","volume":"60","author":"Wu","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01586","article-title":"Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5","volume":"10","author":"Brisse","year":"2019","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/art.41602","article-title":"Study of Tofacitinib in Refractory Dermatomyositis: An Open-Label Pilot Study of Ten Patients","volume":"73","author":"Paik","year":"2021","journal-title":"Arthritis Rheum"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2011.01.009","article-title":"The Type I Interferon System in the Development of Lupus","volume":"23","author":"R\u00f6nnblom","year":"2011","journal-title":"Semin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-014-3012-4","article-title":"Genetic Polymorphisms of dsRNA Ligating Pattern Recognition Receptors TLR3, MDA5, and RIG-I. 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