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Factor H autoantibodies in membranoproliferative glomerulonephritis

Lookup NU author(s): Professor Tim Goodship, Dr Isabel Marchbank, Dr Iain Moore, Dr Eva-Maria Hunze, James Staniforth, Christine Hayes, Professor David Kavanagh, Dr Lisa Turnbull, Dr Kevin 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. (C) 2012 Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Goodship THJ, Pappworth IY, Toth T, Denton M, Houlberg K, McCormick F, Warland D, Moore I, Hunze EM, Staniforth SJ, Hayes C, Cavalcante DP, Kavanagh D, Strain L, Herbert AP, Schmidt CQ, Barlow PN, Harris CL, Marchbank KJ

Publication type: Article

Publication status: Published

Journal: Molecular Immunology

Year: 2012

Volume: 52

Issue: 3-4

Pages: 200-206

Print publication date: 01/10/2012

ISSN (print): 0161-5890

ISSN (electronic): 1872-9142

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/j.molimm.2012.05.009

DOI: 10.1016/j.molimm.2012.05.009


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