{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:19:52Z","timestamp":1773037192053,"version":"3.50.1"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"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:p>IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Its pathogenesis is widely described by a multi-hit hypothesis in which galactose-deficient IgA1 (Gd-IgA1) serves as a central disease driver. Advances in the understanding of IgAN pathophysiology, together with the establishment of proteinuria reduction as a surrogate endpoint in 2019, have led to revisions of recent KDIGO Clinical Practice Guideline. As of 2025, multiple therapeutic agents are under active development and in clinical trials, with several already approved, highlighting the need for individualized treatment strategies. Optimizing the use of these emerging therapies requires a deeper understanding of disease mechanisms. One of the key unresolved questions in pathogenesis of IgAN is why Gd-IgA1-containing immune complexes selectively deposit in the glomerular mesangial region, a disease hallmark of IgAN. Long before the identification of Gd-IgA1, it has been debated whether mesangial immune complex deposition reflects passive trapping of circulating complexes or active deposition mediated by antibodies recognizing glomerular antigens. In this regard, we recently discovered IgA-type anti\u2013mesangial cell antibodies (IgA-MESCA) in serum from patients with IgAN and demonstrated that these antibodies target the mesangial cell\u2013surface antigens \u03b22-spectrin and CBX3. In this review, we summarize evidence from early studies to recent findings, including ours, on autoantibodies in IgAN, with a particular focus on glomerular-specific autoantibodies, and discuss the potential involvement of these autoantibodies in the pathogenesis of IgAN.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1782872","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:29:14Z","timestamp":1773034154000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Autoimmunity in IgA nephropathy"],"prefix":"10.3389","volume":"17","author":[{"given":"Yoshihito","family":"Nihei","sequence":"first","affiliation":[{"name":"Department of Nephrology, Juntendo University Faculty of Medicine","place":["Bunkyo-ku, Tokyo, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Juntendo 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