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In addition, MASLD, along with its more severe form, metabolic dysfunction\u2010associated steatohepatitis (MASH), increases the risk of cardio\u2010metabolic diseases and hepatocellular carcinoma. In recent years, multiple G\u2010protein\u2010coupled receptors (GPCRs) have been identified as potential therapeutic targets for these disorders. Additionally, autoimmunity is believed to potentially play a role in the development of mechanisms contributing to the pathogenesis of MASLD\/MASH. This narrative review examines the diverse autoantibodies associated with the disease, with a particular emphasis on antibodies targeting apolipoprotein A\u20101 (AAA\u20101) and their relationship with anti\u2010GPCRs antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Several autoantibodies have been identified in up to 30% of individuals with MASLD\/MASH, both with and without concomitant autoimmune diseases. Among the anti\u2010GPCR autoantibodies identified in MASLD to date are those targeting the angiotensin II type 1 receptor and the endothelin\u20101 type A receptor. While the contribution of this class of autoantibodies to MASLD\/NASH remains unclear, AAA\u20101 appears to be pathogenic, acting as pro\u2010steatotic and pro\u2010inflammatory mediators. Additionally, current data suggest shared functional responses between anti\u2010GPCR antibodies and AAA1 in cell\u2010based assays used to detect anti\u2010GPCR presence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A better understanding of the role of humoral autoimmunity and the interactions among its various components in the metabolic dysfunction underlying MASLD\/MASH has the potential to open new perspectives for early detection and therapeutic interventions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.70092","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T07:36:24Z","timestamp":1750059384000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Autoimmunity in MASLD: Focus on autoantibodies, anti\u2010apolipoprotein A1 IgG and G protein\u2010coupled 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