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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

Authors :
Christoph Q. Schmidt
Iain Moore
Roy Ward
Lucy V. Holmes
Lynn Morgan
Scott J. Staniforth
Kevin J. Marchbank
Paul N. Barlow
Isabel Y. Pappworth
Lisa Strain
Timothy H.J. Goodship
David J. Kavanagh
Andrew P. Herbert
Source :
Blood. 115:379-387
Publication Year :
2010
Publisher :
American Society of Hematology, 2010.

Abstract

Factor H autoantibodies have been reported in approximately 10% of patients with atypical hemolytic uremic syndrome (aHUS) and are associated with deficiency of factor H–related proteins 1 and 3. In this study we examined the prevalence of factor H autoantibodies in the Newcastle cohort of aHUS patients, determined whether the presence of such autoantibodies is always associated with deficiency of factor H–related proteins 1 and 3, and examined whether such patients have additional susceptibility factors and/or mutations in the genes encoding complement regulator/activators. We screened 142 patients with aHUS and found factor H autoantibodies in 13 individuals (age 1-11 years). The presence of the autoantibodies was confirmed by Western blotting. By using multiplex ligation-dependent probe amplification we measured complement factor H–related (CFHR)1 and CFHR3 copy number. In 10 of the 13 patients there were 0 copies of CFHR1, and in 3 patients there were 2. In 3 of the patients with 0 copies of CFHR1 there was 1 copy of CFHR3, and these individuals exhibited a novel deletion incorporating CFHR1 and CFHR4. In 5 patients mutations were identified: 1 in CFH, 1 in CFI, 1 in CD46, and 2 in C3. The latter observation emphasizes that multiple concurrent factors may be necessary in individual patients for disease manifestation.

Details

ISSN :
15280020 and 00064971
Volume :
115
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....4b56e43b200ee76f8b7b736361a345db
Full Text :
https://doi.org/10.1182/blood-2009-05-221549