{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:22:29Z","timestamp":1793110949601,"version":"4.5.0"},"reference-count":135,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"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>\n                    IgA nephropathy (IgAN) is a mesangioproliferative glomerulonephritis characterized by IgA1-containing immune-complex deposits wherein IgA1 is enriched for galactose-deficient IgA1 (Gd-IgA1) glycoforms. IgAN pathogenesis involves mucosal immune system, as IgAN onset and activity are associated with infections of the upper-respiratory tract, i.e., synpharyngitic hematuria. Current four-hit hypothesis postulates that multiple events, starting with the production of Gd-IgA1, in genetically susceptible individuals lead to the formation of nephritogenic immune complexes and development of IgAN. Biochemical studies using IgA1-producing cell lines derived from the peripheral blood of IgAN patients and healthy controls revealed that secretion of Gd-IgA1 is due to dysregulated expression of several\n                    <jats:italic>O<\/jats:italic>\n                    -glycosylation enzymes. Production of Gd-IgA1 can be further upregulated by some cytokines. Genome-wide association studies identified multiple candidate genes for IgAN, serum levels of IgA, and serum levels of Gd-IgA1. Some of the IgAN-associated genes are also found in other autoimmune diseases and conditions. Notably,\n                    <jats:italic>HORMAD2\/LIF<\/jats:italic>\n                    locus is associated with IgAN, serum levels of IgA, and tonsillectomy. In this review, we detail various findings concerning IgAN and Gd-IgA1 production by cells derived from the circulation and tonsils. Also, as tonsillectomy is commonly used in Japan as a part of treatment for IgAN, we detail biochemical and signaling studies of IgA1-producing cells derived from peripheral blood and tonsils.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1737992","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:41:30Z","timestamp":1769755290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Aberrant signaling in tonsillar B cells producing pathogenic O-glycoforms of IgA1 in IgA nephropathy"],"prefix":"10.3389","volume":"17","author":[{"given":"Koshi","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Nephrology, Juntendo University Faculty of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Ogiwara","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Juntendo University Faculty of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Alabama at Birmingham","place":["Birmingham, AL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Juntendo University Faculty of Medicine","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1012284402054","article-title":"Progress in molecular and genetic studies of IgA nephropathy","volume":"21","author":"Novak","year":"2001","journal-title":"J Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(86)90073-5","article-title":"The human 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