{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:12:01Z","timestamp":1790644321349,"version":"4.1.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"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><jats:title>Objective<\/jats:title><jats:p>To first describe and estimate the potential pathogenic role of Ig4 autoantibodies in complement-mediated thrombotic microangiopathy (TMA) in a patient with IgG4-related disease (IgG4-RD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study is a case report presenting a retrospective review of the patient\u2019s medical chart. Plasma complement C3 and C4 levels, immunoglobulin isotypes and subclasses were determined by nephelometry, the complement pathways\u2019 activity (CH50, AP50, MBL) using WIESLAB<jats:sup>\u00ae<\/jats:sup> Complement System assays. Human complement factor H levels, anti-complement factor H auto-antibodies were analyzed by ELISA, using HRP-labeled secondary antibodies specific for human IgG, IgG4, and IgA, respectively. Genetic analyses were performed by exome sequencing of 14 gens implicated in complement disorders, as well as multiplex ligation-dependent probe amplification looking specifically for <jats:italic>CFH, CFHR1-2-3, and 5<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our brief report presents the first case of IgG4-RD with complement-mediated TMA originating from both pathogenic <jats:italic>CFHR<\/jats:italic> 1 and <jats:italic>CFHR<\/jats:italic> 4 genes deletions, and inhibitory anti-complement factor H autoantibodies of the IgG4 subclass. Remission was achieved with plasmaphereses, corticosteroids, and cyclophosphamide. Following remission, the patient was diagnosed with lymphocytic meningitis and SARS-CoV-2 pneumonia with an uneventful recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IgG4-RD can be associated with pathogenic IgG4 autoantibodies. Genetic predisposition such as <jats:italic>CFHR<\/jats:italic>1 and <jats:italic>CFHR<\/jats:italic>4 gene deletions enhance the susceptibility to the formation of inhibitory anti-Factor H IgG4 antibodies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2020.604759","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T14:30:03Z","timestamp":1613226603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Case Report: Severe Complement-Mediated Thrombotic Microangiopathy in IgG4-Related Disease Secondary to Anti-Factor H IgG4 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