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In systemic lupus erythematosus (SLE), mitochondria and their inner components are released into the extracellular space, potentially eliciting a proinflammatory response from the immune system. While cardiolipin and mitochondrial DNA and RNA are confirmed targets of autoantibodies, other antigenic mitochondrial proteins in SLE remain to be identified. The present study was undertaken to characterize the protein repertoire recognized by antimitochondrial antibodies (AMAs) in patients with SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using shotgun proteomic profiling, we identified 1,345 proteins, 431 of which were associated with the mitochondrial proteome. Immunoreactivities to several of these candidate proteins were assessed in serum samples from a local cohort (n\u2009=\u200930 healthy donors and 87 patients with SLE) using enzyme\u2010linked immunosorbent assay, and further analyzed for associations with demographic and disease characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We determined that IgG antibodies to the complement component C1q binding protein were significantly elevated in the patients with SLE (<jats:italic>P<\/jats:italic>\u00a0=\u20090.049) and were also associated with lupus anticoagulant positivity (<jats:italic>P<\/jats:italic>\u00a0=\u20090.049). Elevated levels of IgG antibodies against mitochondrial protein mitofusin 1 (MFN\u20101) were promising predictors of SLE diagnosis in our cohort (adjusted odds ratio 2.99 [95% confidence interval 1.39\u20136.43], <jats:italic>P<\/jats:italic>\u00a0=\u20090.0044). Moreover, increased levels of anti\u2013MFN\u20101 were associated with the presence of antiphospholipids (<jats:italic>P<\/jats:italic>\u00a0=\u20090.011) and anti\u2013double\u2010stranded DNA (<jats:italic>P<\/jats:italic>\u00a0=\u20090.0005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this study, we characterized the mitochondrial repertoire targeted by AMAs in the setting of SLE. Our results indicate that autoantibodies can recognize secreted and\/or surface proteins of mitochondrial origin. Profiling of the AMA repertoire in large prospective cohorts may improve our knowledge of mitochondrial biomarkers and their usefulness for patient stratification.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42082","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T02:33:30Z","timestamp":1644201210000},"page":"1193-1203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Identification of Mitofusin 1 and Complement Component 1q Subcomponent Binding Protein as Mitochondrial Targets in Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-6727","authenticated-orcid":false,"given":"Yann L. 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