Factor H autoantibodies in membranoproliferative glomerulonephritis

Timothy H. J. Goodship, Isabel Y. Pappworth, Tibor Toth, Mark Denton, Kris Houlberg, Frances McCormick, David Warland, Iain Moore, Eva-Maria Hunze, Scott J. Staniforth, Christine Hayes, Danielle Paixao Cavalcante, David Kavanagh, Lisa Strain, Andrew P. Herbert, Christoph Q. Schmidt, Paul N. Barlow, Claire L. Harris, Kevin J. Marchbank

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Abstract

Factor H autoantibodies are found in similar to 10% of aHUS patients. Most are associated with complete deficiency of factor H related proteins 1/3 and bind to the C terminal recognition domain. MPGN, like aHUS, is characterised by complement activation. In this study we, therefore, examined the hypothesis that factor H autoantibodies are associated with MPGN. We screened sera from 16 MPGN patients and 100 normal controls using ELISA and detected strongly positive IgG factor H autoantibodies in 2 patients. One patient had type II (DDD) MPGN (male aged 24 yrs) with C3NeF and the other type I (female aged 26 yrs) with no detectable C3NeF. We identified the binding site of the autoantibodies using small SCR domain fragments in the ELISA and showed that the autoantibodies in both patients bound predominately to the N terminal complement regulatory domain of factor H. We measured CFHR1/3 copy number using MLPA and showed that both patients had 2 copies of CFHR1 and 3. Finally, we examined the functionality of detected factor H autoantibodies using purified patient IgG and observed increased haemolysis when purified IgG from both patients was added to normal human sera prior to incubation with rabbit red blood cells. Thus, in a cohort of MPGN patients we have found a high titre of functionally significant factor H autoantibodies in two patients with MPGN. Antibody depleting therapy may have a role in such patients and we suggest that screening for factor H autoantibodies should be undertaken in all patients with MPGN.

Original languageEnglish
Pages (from-to)200-206
Number of pages7
JournalMolecular Immunology
Volume52
Issue number3-4
Early online date20 Jun 2012
DOIs
Publication statusPublished - 31 Dec 2012

Keywords

  • Factor H
  • Complement
  • MPGN
  • Autoantibodies

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