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Lookup NU author(s): Dr Isabel Pappworth,
Professor David KavanaghORCiD,
Dr Iain Moore,
Dr Lisa Turnbull
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Factor H autoantibodies are found in not, vert, similar10% of atypical haemolytic uraemic syndrome (aHUS) patients. The majority are associated with complete deficiency of factor H related proteins 1/3 and bind to the C terminal recognition domain. Membranoproliferative glomerulonephritis (MPGN), like aHUS, is characterised by complement activation. Therefore, we examined the hypothesis that factor H autoantibodies are associated with MPGN. We screened sera from 14 MPGN patients and 100 normal controls for factor H autoantibodies using enzyme-linked immunosorbent assay (ELISA). We detected strongly positive IgG factor H autoantibodies in two patients, which were confirmed by titration and western blotting. Further serum samples collected from both confirmed these findings and in one showed an increasing antibody titre with time. One patient (male aged 24 years) had type II (dense deposit disease; DDD) MPGN and one patient (female aged 26 years) had type I MPGN and both were C3 NeF negative. 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 in paired DNA samples using multiplex ligation-dependent probe amplification (MLPA) and established both patients had two copies of CFHR1/3. Finally, functionality of the detected factor H autoantibodies was examined using purified patient IgG in haemolytic assays. We observed increased haemolysis when purified Ig from both patients (but not from control) was added to normal human sera prior to incubation with rabbit red blood cells. Thus, in a small cohort of MPGN patients, we have found a high titre of functionally significant factor H autoantibodies in two patients. 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 (particularly DDD).
Author(s): Pappworth IY, Denton M, Kavanagh D, Moore I, Strain L, Barlow PN, Herbert AP, Schmidt CQ
Publication type: Conference Proceedings (inc. Abstract)
Publication status: Published
Conference Name: Molecular Immunology: 23rd International National Complement Workshop
Year of Conference: 2010
Pages: 2291-2291 no. 91
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