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

Iain Moore, Lisa Strain, Isabel Pappworth, David Kavanagh, Paul N. Barlow, Andrew P. Herbert, Christoph Q. Schmidt, Scott J. Staniforth, Lucy V. Holmes, Roy Ward, Lynn Morgan, Timothy H. J. Goodship, Kevin J. Marchbank

Research output: Contribution to journalArticlepeer-review

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.
Original languageUndefined/Unknown
Pages (from-to)379-387
Number of pages9
JournalBlood
Volume115
Issue number2
Early online date27 Oct 2009
DOIs
Publication statusPublished - 14 Jan 2010

Keywords

  • atypical hemolytic-uremic syndrome
  • autoantibodies
  • cd46 antigen
  • complement factor h
  • cultural formulation interview
  • mutation

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