Factor H autoantibodies in membranoproliferative glomerulonephritis.
Factor H autoantibodies are found in ~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 CFHR 1/3 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.
Institutes of Cellular Medicine and Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. t.h.j.goodship@ncl.ac.uk
Timothy H J
TH
Goodship
Isabel Y
IY
Pappworth
Tibor
T
Toth
Mark
M
Denton
Kris
K
Houlberg
Frances
F
McCormick
David
D
Warland
Iain
I
Moore
Eva-Maria
EM
Hunze
Scott J
SJ
Staniforth
Christine
C
Hayes
Danielle Paixão
DP
Cavalcante
David
D
Kavanagh
Lisa
L
Strain
Andrew P
AP
Herbert
Christoph Q
CQ
Schmidt
Paul N
PN
Barlow
Claire L
CL
Harris
Kevin J
KJ
Marchbank
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D001666:Binding Sites, Antibody; D003176:Complement C3; D003178:Complement C3 Nephritic Factor / Q000032:analysis; D017242:Complement Factor H / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D001323:Autoantibodies; D003176:Complement C3; D003178:Complement C3 Nephritic Factor; D017242:Complement Factor H