{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T04:16:43Z","timestamp":1743221803994,"version":"3.40.3"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The noncollagenous (NC1) domains of \u03b13\u03b14\u03b15(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport posttransplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of \u03b13\u03b14\u03b15NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM Abs. Alport alloantibodies, which bound to native murine \u03b13\u03b14\u03b15NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b\u2212\/\u2212 mice susceptible to Ab-mediated inflammation. Goodpasture autoantibodies, which bound to murine \u03b13NC1 monomer and dimer subunits but not to native \u03b13\u03b14\u03b15NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 crosslinks, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked \u03b13NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys, a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of \u03b13\u03b14\u03b15NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by posttranslational modifications of an autoantigen.<\/jats:p>","DOI":"10.4049\/jimmunol.1001152","type":"journal-article","created":{"date-parts":[[2010,8,14]],"date-time":"2010-08-14T02:20:16Z","timestamp":1281752416000},"page":"3520-3528","source":"Crossref","is-referenced-by-count":21,"title":["Alport Alloantibodies but Not Goodpasture Autoantibodies Induce Murine Glomerulonephritis: Protection by Quinary Crosslinks Locking Cryptic \u03b13(IV) Collagen Autoepitopes In Vivo"],"prefix":"10.1093","volume":"185","author":[{"given":"Wentian","family":"Luo","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu-Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford E","family":"Kashtan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School , Minneapolis, MN 55455"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorin-Bogdan","family":"Borza","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine , Nashville, TN 37232"},{"name":"Department of Pathology, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,9,15]]},"reference":[{"key":"2025032411533210400_r1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/ni772","article-title":"How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease","volume":"3","author":"Matsumoto","year":"2002","journal-title":"Nat. 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