{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:53:15Z","timestamp":1792842795195,"version":"4.5.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: C3 glomerulopathy (C3G) is caused by overactivity of the alternative pathway of complement that results in bright glomerular C3 staining with minimal or no deposition of immunoglobulins on immunofluorescence microscopy. Laser microdissection and mass spectrometry of the two subtypes, C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), have identified C3 as the predominant glomerular complement protein, although lesser amounts of C9, C5, C6, C7 and C8 are detectable. C3 plays a central role in complement activity, with its proteolytic cleavage first generating C3a and C3b, followed by inactivation of C3b generating iC3b (which includes C3\u03b1 and C3\u03b2), which undergoes further breakdown yielding C3c and terminal breakdown fragment C3dg. The composition of C3 breakdown products in C3G is not known.<\/jats:p>\n                  <jats:p>Methods: In this study, we chose six cases each of C3GN and DDD to analyze the composition of C3 deposits. We analyzed the amino acid sequence of C3 spectra detected by mass spectrometry to determine the relative abundance of C3 fragments in C3G. Thus we were able to determine the amino acid sequences mapping to the various C3 activation products including C3dg, C3\u03b1 (C3\u03b11 and \u03b12), and C3\u03b2 that are part of C3b\/iC3b\/C3c.<\/jats:p>\n                  <jats:p>Results: C3dg is the predominant cleavage product detected with the highest amino acid coverage. The remaining amino acids map to C3\u03b1 (C3\u03b11 and \u03b12) and C3\u03b2. Amino acids mapping to C3a and C3f are absent. Taken together, the C3\u03b1 and C3\u03b2 amino acids represent iC3b prior to or after C3c cleavage of C3dg. The C3 spectra for both C3GN and DDD are surprisingly similar.<\/jats:p>\n                  <jats:p>Conclusion: The finding of large amounts of C3dg suggests that C3b deposition in the glomerulus is an active process triggered by thioester binding of C3b to the glycocalyx overlying the glomerular endothelial cells and glomerular basement membrane. Regulatory protein-mediated inactivation of C3b results in the generation of iC3b. After additional cleavages, mostly C3dg remains.<\/jats:p>","DOI":"10.1093\/ndt\/gfw290","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T20:33:06Z","timestamp":1470774786000},"page":"459-465","source":"Crossref","is-referenced-by-count":26,"title":["Characterization of C3 in C3 glomerulopathy"],"prefix":"10.1093","volume":"32","author":[{"given":"Sanjeev","family":"Sethi","sequence":"first","affiliation":[{"name":"1Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Vrana","sequence":"additional","affiliation":[{"name":"1Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando C.","family":"Fervenza","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Theis","sequence":"additional","affiliation":[{"name":"1Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Sethi","sequence":"additional","affiliation":[{"name":"3Mayo High School, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Kurtin","sequence":"additional","affiliation":[{"name":"1Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"4Molecular Otolaryngology and Renal Research Laboratories, Departments of Internal Medicine and Pediatrics, Division of Nephrology, Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.H.","family":"Smith","sequence":"additional","affiliation":[{"name":"4Molecular Otolaryngology and Renal Research Laboratories, Departments of Internal Medicine and Pediatrics, Division of Nephrology, Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,8,9]]},"reference":[{"key":"2025102312500170600_gfw290C1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1136\/jmg.2006.045328","article-title":"Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome","volume":"44","author":"Servais","year":"2007","journal-title":"J Med 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