Factor i autoantibodies in patients with atypical hemolytic uremic syndrome: Disease-associated or an epiphenomenon?

David Kavanagh, Isabel Y. Pappworth, Holly Anderson, Christine M. Hayes, Iain Moore, Eva Maria Hunze, Karim Bennaceur, Pietro Roversi, Susan Lea, Lisa Strain, Roy Ward, Nick Plant, Corina Nailescu, Timothy H J Goodship, Kevin J. Marchbank

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background and objectives: Atypical hemolytic uremic syndrome is a disease associated with mutations in the genes encoding the complement regulators factors H and I. In addition, factor H autoantibodies have been reported in ∼10% of patients with atypical hemolytic uremic syndrome. This study searched for the presence of factor I autoantibodies in atypical hemolytic uremic syndrome. Design, setting, participants, & measurements: This study screened 175 atypical hemolytic uremic syndrome patients for factor I autoantibodies using ELISA with confirmatory Western blotting. Functional studies using purified immunoglobulin from one patient were subsequently undertaken. Results: Factor I autoantibodies were detected in three patients. In one patient with a high titer of autoantibody, the titer was tracked over time and was found to have no association with disease activity. This study found evidence of an immune complex of antibody and factor I in this patient, but purified IgG, isolated from current serum samples, had only a minor effect on fluid phase and cell surface complement regulation. Genetic analysis of the three patients with factor I autoantibodies revealed that they had two copies of the genes encoding factor H-related proteins 1 and 3 and therefore, did not have a deletion commonly associated with factor H autoantibodies in atypical hemolytic uremic syndrome. Two patients, however, had functionally significant mutations in complement factor H. Conclusions: These findings reinforce the concept of multiple concurrent risk factors being associated with atypical hemolytic uremic syndrome but question whether autoantibodies per se predispose to atypical hemolytic uremic syndrome.

Original languageEnglish
Pages (from-to)417-426
Number of pages10
JournalClinical Journal of the American Society of Nephrology
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2012

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Autoantibodies
Complement Factor H
Complement Factor I
Mutation
Atypical Hemolytic Uremic Syndrome
Immunologic Factors
Antigen-Antibody Complex
Genes
Immunoglobulins
Immunoglobulin G
Western Blotting
Enzyme-Linked Immunosorbent Assay
Antibodies
Serum

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Epidemiology
  • Critical Care and Intensive Care Medicine

Cite this

Factor i autoantibodies in patients with atypical hemolytic uremic syndrome : Disease-associated or an epiphenomenon? / Kavanagh, David; Pappworth, Isabel Y.; Anderson, Holly; Hayes, Christine M.; Moore, Iain; Hunze, Eva Maria; Bennaceur, Karim; Roversi, Pietro; Lea, Susan; Strain, Lisa; Ward, Roy; Plant, Nick; Nailescu, Corina; Goodship, Timothy H J; Marchbank, Kevin J.

In: Clinical Journal of the American Society of Nephrology, Vol. 7, No. 3, 01.03.2012, p. 417-426.

Research output: Contribution to journalArticle

Kavanagh, D, Pappworth, IY, Anderson, H, Hayes, CM, Moore, I, Hunze, EM, Bennaceur, K, Roversi, P, Lea, S, Strain, L, Ward, R, Plant, N, Nailescu, C, Goodship, THJ & Marchbank, KJ 2012, 'Factor i autoantibodies in patients with atypical hemolytic uremic syndrome: Disease-associated or an epiphenomenon?', Clinical Journal of the American Society of Nephrology, vol. 7, no. 3, pp. 417-426. https://doi.org/10.2215/CJN.05750611
Kavanagh, David ; Pappworth, Isabel Y. ; Anderson, Holly ; Hayes, Christine M. ; Moore, Iain ; Hunze, Eva Maria ; Bennaceur, Karim ; Roversi, Pietro ; Lea, Susan ; Strain, Lisa ; Ward, Roy ; Plant, Nick ; Nailescu, Corina ; Goodship, Timothy H J ; Marchbank, Kevin J. / Factor i autoantibodies in patients with atypical hemolytic uremic syndrome : Disease-associated or an epiphenomenon?. In: Clinical Journal of the American Society of Nephrology. 2012 ; Vol. 7, No. 3. pp. 417-426.
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