{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:29:39Z","timestamp":1791289779239,"version":"4.3.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"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":[[2012,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complement is a major innate immune surveillance system. One of its most important regulators is the plasma protein factor H (FH). FH inactivation by mutations or by autoantibodies is associated with a thrombotic microangiopathy disease, atypical hemolytic uremic syndrome. In this study, we report the characterization of blood samples from 19 anti-FH Ab-positive atypical hemolytic uremic syndrome patients collected at the acute phase of the disease. Analyses of the functional consequences and epitope mapping, using both fluid phase and solid phase approaches, were performed. The anti-FH Abs perturbed FH-mediated cell protection (100%), inhibited FH interaction with C3 (46%), and caused C3 consumption (47%). The Abs were directed against multiple FH epitopes located at the N and C termini. In all tested patients, high titers of FH-containing circulating immune complexes were detected. The circulating immune complex titers correlated with the disease stage better than did the Ab titers. Our results show that anti-FH autoantibodies induce neutralization of FH at acute phase of the disease, leading to an overall impairment of several functions of FH, extending the role of autoantibodies beyond the impairment of the direct cell surface protection.<\/jats:p>","DOI":"10.4049\/jimmunol.1200679","type":"journal-article","created":{"date-parts":[[2012,8,25]],"date-time":"2012-08-25T00:05:56Z","timestamp":1345853156000},"page":"3528-3537","source":"Crossref","is-referenced-by-count":98,"title":["Overall Neutralization of Complement Factor H by Autoantibodies in the Acute Phase of the Autoimmune Form of Atypical Hemolytic Uremic Syndrome"],"prefix":"10.1093","volume":"189","author":[{"given":"Caroline","family":"Blanc","sequence":"first","affiliation":[{"name":"INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers , 75006 Paris,","place":["France"]},{"name":"Universit\u00e9 Paris Diderot , 75013 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubka T","family":"Roumenina","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers , 75006 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahya","family":"Ashraf","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers , 75006 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satu","family":"Hyv\u00e4rinen","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki , FI-00014 Helsinki,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidharth Kumar","family":"Sethi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences , New Delhi 110029,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Ranchin","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies R\u00e9nales Rares \u201cN\u00e9phrogones,\u201d Service de N\u00e9phrologie et Rhumatologie P\u00e9diatrique, H\u00f4pital Femme M\u00e8re Enfant, Hospices Civils de Lyon , 69677 Bron Cedex,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Niaudet","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie P\u00e9diatrique, H\u00f4pital Necker-Enfants Malades, Assistance Publique\u2013H\u00f4pitaux de Paris , 75743 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Loirat","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie, H\u00f4pital Robert Debr\u00e9, Assistance Publique\u2013H\u00f4pitaux de Paris, Universit\u00e9 Paris\u2013Diderot , 75019 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashima","family":"Gulati","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences , New Delhi 110029,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Bagga","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, All India Institute of Medical Sciences , New Delhi 110029,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf Herman","family":"Fridman","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers , 75006 Paris,","place":["France"]},{"name":"Service d\u2019Immunologie Biologique, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance Publique\u2013H\u00f4pitaux de Paris , 75908 Paris,","place":["France"]},{"name":"Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine , 75006 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Saut\u00e8s-Fridman","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers , 75006 Paris,","place":["France"]},{"name":"Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine , 75006 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Sakari","family":"Jokiranta","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki , FI-00014 Helsinki,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Fr\u00e9meaux-Bacchi","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers , 75006 Paris,","place":["France"]},{"name":"Service d\u2019Immunologie Biologique, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance Publique\u2013H\u00f4pitaux de Paris , 75908 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Agn\u00e8s","family":"Dragon-Durey","sequence":"additional","affiliation":[{"name":"INSERM Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers , 75006 Paris,","place":["France"]},{"name":"Service d\u2019Immunologie Biologique, H\u00f4pital Europ\u00e9en Georges Pompidou, Assistance Publique\u2013H\u00f4pitaux de Paris , 75908 Paris,","place":["France"]},{"name":"Universit\u00e9 Paris Descartes, Facult\u00e9 de M\u00e9decine , 75006 Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,10,1]]},"reference":[{"key":"2025032409272084600_r1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025032409272084600_r2","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJMra0902814","article-title":"Atypical hemolytic-uremic syndrome","volume":"361","author":"Noris","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"2025032409272084600_r3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00281-005-0003-2","article-title":"Atypical haemolytic uraemic syndrome and mutations in complement regulator genes","volume":"27","author":"Dragon-Durey","year":"2005","journal-title":"Springer Semin. Immunopathol."},{"key":"2025032409272084600_r4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jim.2010.12.020","article-title":"Alternative complement pathway assessment in patients with atypical HUS","volume":"365","author":"Roumenina","year":"2011","journal-title":"J. Immunol. Methods"},{"key":"2025032409272084600_r5","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1681\/ASN.2004050380","article-title":"Anti-factor H autoantibodies associated with atypical hemolytic uremic syndrome","volume":"16","author":"Dragon-Durey","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"2025032409272084600_r6","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1681\/ASN.2010030315","article-title":"Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome","volume":"21","author":"Dragon-Durey","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"2025032409272084600_r7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.molimm.2004.02.005","article-title":"The human complement factor H: functional roles, genetic variations and disease associations","volume":"41","author":"Rodr\u00edguez de C\u00f3rdoba","year":"2004","journal-title":"Mol. Immunol."},{"key":"2025032409272084600_r8","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.4049\/jimmunol.181.4.2610","article-title":"A new map of glycosaminoglycan and C3b binding sites on factor H","volume":"181","author":"Schmidt","year":"2008","journal-title":"J. Immunol."},{"key":"2025032409272084600_r9","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.molimm.2010.03.007","article-title":"Both domain 19 and domain 20 of factor H are involved in binding to complement C3b and C3d","volume":"47","author":"Bhattacharjee","year":"2010","journal-title":"Mol. Immunol."},{"key":"2025032409272084600_r10","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1073\/pnas.1017087108","article-title":"Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement","volume":"108","author":"Kajander","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409272084600_r11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nsmb.2018","article-title":"Structural basis for engagement by complement factor H of C3b on a self surface","volume":"18","author":"Morgan","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2025032409272084600_r12","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1182\/blood-2007-09-109876","article-title":"Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1\/CFHR3 deficiency","volume":"111","author":"J\u00f3zsi","year":"2008","journal-title":"Blood"},{"key":"2025032409272084600_r13","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1182\/blood-2009-05-221549","article-title":"Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome","volume":"115","author":"Moore","year":"2010","journal-title":"Blood"},{"key":"2025032409272084600_r14","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1136\/jmg.2008.064766","article-title":"The high frequency of complement factor H related CFHR1 gene deletion is restricted to specific subgroups of patients with atypical haemolytic uraemic syndrome","volume":"46","author":"Dragon-Durey","year":"2009","journal-title":"J. Med. Genet."},{"key":"2025032409272084600_r15","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1182\/blood-2009-02-205641","article-title":"Factor H-related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation","volume":"114","author":"Heinen","year":"2009","journal-title":"Blood"},{"key":"2025032409272084600_r16","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/j.molimm.2011.06.245","article-title":"Human complement factor H-related protein 2 (CFHR2) represents a novel complement regulator, which is reduced in a patient with MPGN I","volume":"48","author":"Eberhardt","year":"2011","journal-title":"Mol. Immunol."},{"key":"2025032409272084600_r17","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1371\/journal.pgen.0030041","article-title":"Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome","volume":"3","author":"Zipfel","year":"2007","journal-title":"PLoS Genet."},{"key":"2025032409272084600_r18","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1182\/blood-2007-02-071472","article-title":"Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome","volume":"110","author":"J\u00f3zsi","year":"2007","journal-title":"Blood"},{"key":"2025032409272084600_r19","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/ndt\/gfp388","article-title":"Functional analyses indicate a pathogenic role of factor H autoantibodies in atypical haemolytic uraemic syndrome","volume":"25","author":"Strobel","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"2025032409272084600_r20","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/ki.2011.152","article-title":"Factor H-related protein 1 neutralizes anti-factor H autoantibodies in autoimmune hemolytic uremic syndrome","volume":"80","author":"Strobel","year":"2011","journal-title":"Kidney Int."},{"key":"2025032409272084600_r21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.molimm.2004.01.003","article-title":"Functional analysis in serum from atypical hemolytic uremic syndrome patients reveals impaired protection of host cells associated with mutations in factor H","volume":"41","author":"S\u00e1nchez-Corral","year":"2004","journal-title":"Mol. Immunol."},{"key":"2025032409272084600_r22","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1038\/sj.emboj.7601052","article-title":"Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome","volume":"25","author":"Jokiranta","year":"2006","journal-title":"EMBO J."},{"key":"2025032409272084600_r23","doi-asserted-by":"crossref","first-page":"11082","DOI":"10.1074\/jbc.M110.211839","article-title":"Disease-associated N-terminal complement factor H mutations perturb cofactor and decay-accelerating activities","volume":"286","author":"Pechtl","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2025032409272084600_r24","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/humu.20435","article-title":"The interactive factor H-atypical hemolytic uremic syndrome mutation database and website: update and integration of membrane cofactor protein and factor I mutations with structural models","volume":"28","author":"Saunders","year":"2007","journal-title":"Hum. Mutat."},{"key":"2025032409272084600_r25","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1681\/ASN.2005080868","article-title":"Factor H and atypical hemolytic uremic syndrome: mutations in the C-terminus cause structural changes and defective recognition functions","volume":"17","author":"J\u00f3zsi","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"2025032409272084600_r26","doi-asserted-by":"crossref","first-page":"27657","DOI":"10.1074\/jbc.M002903200","article-title":"Each of the three binding sites on complement factor H interacts with a distinct site on C3b","volume":"275","author":"Jokiranta","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2025032409272084600_r27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0022-1759(02)00296-X","article-title":"Concerted clearance of immune complexes bound to the human erythrocyte complement receptor: development of a heterologous mouse model","volume":"270","author":"Henderson","year":"2002","journal-title":"J. Immunol. Methods"},{"key":"2025032409272084600_r28","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.autrev.2007.01.017","article-title":"Immune complex clearance by monocytes and macrophages in systemic lupus erythematosus","volume":"6","author":"Kavai","year":"2007","journal-title":"Autoimmun. Rev."},{"key":"2025032409272084600_r29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.autrev.2008.06.002","article-title":"Immune complex clearance by complement receptor type 1 in SLE","volume":"8","author":"Kavai","year":"2008","journal-title":"Autoimmun. Rev."},{"key":"2025032409272084600_r30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.blre.2009.11.001","article-title":"Inhibitory anti-ADAMTS 13 antibodies: measurement and clinical application","volume":"24","author":"Scully","year":"2010","journal-title":"Blood Rev."},{"key":"2025032409272084600_r31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/B978-0-12-387025-4.00003-0","article-title":"Acquired hemophilia A","volume":"54","author":"Franchini","year":"2011","journal-title":"Adv. Clin. Chem."},{"key":"2025032409272084600_r32","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1055\/s-0030-1262885","article-title":"Anti-factor H autoantibody-associated hemolytic uremic syndrome: review of literature of the autoimmune form of HUS","volume":"36","author":"Dragon-Durey","year":"2010","journal-title":"Semin. Thromb. Hemost."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/7\/3528\/61725531\/1200679.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/7\/3528\/61725531\/1200679.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T03:17:19Z","timestamp":1743045439000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/189\/7\/3528\/7994746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,1]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,10,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1200679","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717957713.793462108","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,10]]},"published":{"date-parts":[[2012,10,1]]}}}