{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:14:08Z","timestamp":1790291648088,"version":"4.1.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>Crescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One hundred IgAN patients with various proportions of crescents\u201424 with 1%\u201324%, 27 with 25%\u201349%, 21 with 50%\u201374% 12 with more than 75%, and 16 without crescents\u2014were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a\/creatinine (C3a\/Cr): 6.7295 ng\/mg, interquartile range (IQR) 1.4652\u201362.1086 ng\/mg vs. 0.1055 ng\/mg, IQR 0\u20131.4089 ng\/mg; urinary C5a\/Cr: 15.6202 ng\/mg, 4.3127\u201366.7347 ng\/mg vs. 0.3280 ng\/mg, IQR 0.0859\u20132.4439 ng\/mg; urinary sC5b-9\/Cr: 98.6357 ng\/mg, 8.8058\u20131,087.4578 ng\/mg vs. 1.4262 ng\/mg, 0.0916\u201311.0858 ng\/mg, all <jats:italic>p<\/jats:italic>-values &amp;lt;0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both <jats:italic>p<\/jats:italic>-values &amp;lt;0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (<jats:italic>p<\/jats:italic> = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Excess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.676919","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T06:15:30Z","timestamp":1631600130000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Complement Activation Is Associated With Crescents in IgA Nephropathy"],"prefix":"10.3389","volume":"12","author":[{"given":"Zi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manliu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jicheng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020109","article-title":"IgA Nephropathy","volume":"347","author":"Donadio","year":"2002","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(88)80021-0","article-title":"Worldwide Perspective of IgA Nephropathy","volume":"12","author":"Levy","year":"1988","journal-title":"Am J Kidney Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"16001","DOI":"10.1038\/nrdp.2016.1","article-title":"IgA Nephropathy","volume":"2","author":"Lai","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016040433","article-title":"A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy","volume":"28","author":"Haas","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012101017","article-title":"Prediction of Outcomes in Crescentic IgA Nephropathy in a Multicenter Cohort Study","volume":"24","author":"Lv","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.kint.2018.03.009","article-title":"IgA Nephropathy: New Insights Into the Role of Complement","volume":"94","author":"Floege","year":"2018","journal-title":"Kidney Int"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014101000","article-title":"Current Understanding of the Role of Complement in IgA Nephropathy","volume":"26","author":"Maillard","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(88)80042-8","article-title":"Activation of Complement in IgA Nephropathy","volume":"12","author":"Wyatt","year":"1988","journal-title":"Am J Kidney Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005090923","article-title":"Glomerular Activation of the Lectin Pathway of Complement in IgA Nephropathy Is Associated With More Severe Renal Disease","volume":"17","author":"Roos","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(88)80022-2","article-title":"The Immunohistology of IgA Nephropathy","volume":"12","author":"Jennette","year":"1988","journal-title":"Am J Kidney Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464410X.1984.tb06161.x","article-title":"Glomerular Deposition and Serum Levels of Complement Control Proteins in Patients With IgA Nephropathy","volume":"21","author":"Miyazaki","year":"1984","journal-title":"Clin Nephrol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2001.28611","article-title":"Mesangial IgA2 Deposits and Lectin Pathway-Mediated Complement Activation in IgA Glomerulonephritis","volume":"38","author":"Hisano","year":"2001","journal-title":"Am J Kidney Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1159\/000045212","article-title":"Deposition of Mannan Binding Protein and Mannan Binding Protein-Mediated Complement Activation in the Glomeruli of Patients With IgA Nephropathy","volume":"80","author":"Matsuda","year":"1998","journal-title":"Nephron"},{"key":"B14","doi-asserted-by":"publisher","first-page":"897","DOI":"10.2215\/CJN.09710913","article-title":"Association of C4d Deposition With Clinical Outcomes in IgA Nephropathy","volume":"9","author":"Espinosa","year":"2014","journal-title":"Clin J Am Soc Nephrol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3632","article-title":"Prognostic Value of Glomerular C4d Staining in Patients With IgA Nephritis","volume":"7","author":"Sahin","year":"2014","journal-title":"Int J Clin Exp Pathol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/ckj\/sfv076","article-title":"Use of Eculizumab in Crescentic IgA Nephropathy: Proof of Principle and Conundrum","author":"Troels","year":"2015","journal-title":"Clin Kidney J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-014-2863-y","article-title":"Eculizumab Treatment for Rescue of Renal Function in IgA Nephropathy[J]","volume":"29","author":"Rosenblad","year":"2014","journal-title":"Pediatr Nephrol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.676919\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T06:15:33Z","timestamp":1631600133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.676919\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":17,"alternative-id":["10.3389\/fimmu.2021.676919"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.676919","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,14]]},"article-number":"676919"}}