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Analysis of genes coding for CD46, CD55 and C4b-binding protein in patients with idiopathic, recurrent, spontaneous pregnancy loss.

Mohlin, Frida LU ; Mercier, Eric ; Fremeaux-Bacchi, Veronique ; Liszewski, M Kathryn ; Atkinson, John P ; Gris, Jean-Christophe and Blom, Anna LU orcid (2013) In European Journal of Immunology 43(6). p.1617-1629
Abstract
Since a tightly regulated complement system is needed for a successful pregnancy, we hypothesized that alterations in complement inhibitors may be associated with idiopathic, recurrent miscarriage. We sequenced all exons coding for three complement inhibitors: C4b-binding protein (C4BP), CD46 and CD55 in 384 childless women with at least two miscarriages that could not be explained by known risk factors. Several alterations were found in C4BPA, of which the R120H, I126T, and the G423T mutations affected the expression level and/or the ability of recombinant C4BP to serve as cofactor for factor I. The only variant in C4BPB was located in the C-terminal part, and did not impair the polymerization of the molecule. Our results identify for the... (More)
Since a tightly regulated complement system is needed for a successful pregnancy, we hypothesized that alterations in complement inhibitors may be associated with idiopathic, recurrent miscarriage. We sequenced all exons coding for three complement inhibitors: C4b-binding protein (C4BP), CD46 and CD55 in 384 childless women with at least two miscarriages that could not be explained by known risk factors. Several alterations were found in C4BPA, of which the R120H, I126T, and the G423T mutations affected the expression level and/or the ability of recombinant C4BP to serve as cofactor for factor I. The only variant in C4BPB was located in the C-terminal part, and did not impair the polymerization of the molecule. Our results identify for the first time alterations in C4BP in women experiencing recurrent miscarriages. We also found four CD46 alterations in individual patients that were not found in healthy controls. One of the rare variants, P324L, showed decreased expression, whereas N213I resulted in deficient protein processing as well as an impaired cofactor activity in the degradation of both C4b and C3b. The identified alterations may result in in vivo consequences and contribute to the disorder but the degree of association must be evaluated in larger cohorts. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Immunology
volume
43
issue
6
pages
1617 - 1629
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000320785700029
  • pmid:23508668
  • scopus:84879469163
  • pmid:23508668
ISSN
1521-4141
DOI
10.1002/eji.201243196
language
English
LU publication?
yes
id
b0e4a74a-fb80-466e-b5b1-b579bc88186b (old id 3627999)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23508668?dopt=Abstract
date added to LUP
2016-04-01 10:29:19
date last changed
2022-05-13 17:29:01
@article{b0e4a74a-fb80-466e-b5b1-b579bc88186b,
  abstract     = {{Since a tightly regulated complement system is needed for a successful pregnancy, we hypothesized that alterations in complement inhibitors may be associated with idiopathic, recurrent miscarriage. We sequenced all exons coding for three complement inhibitors: C4b-binding protein (C4BP), CD46 and CD55 in 384 childless women with at least two miscarriages that could not be explained by known risk factors. Several alterations were found in C4BPA, of which the R120H, I126T, and the G423T mutations affected the expression level and/or the ability of recombinant C4BP to serve as cofactor for factor I. The only variant in C4BPB was located in the C-terminal part, and did not impair the polymerization of the molecule. Our results identify for the first time alterations in C4BP in women experiencing recurrent miscarriages. We also found four CD46 alterations in individual patients that were not found in healthy controls. One of the rare variants, P324L, showed decreased expression, whereas N213I resulted in deficient protein processing as well as an impaired cofactor activity in the degradation of both C4b and C3b. The identified alterations may result in in vivo consequences and contribute to the disorder but the degree of association must be evaluated in larger cohorts.}},
  author       = {{Mohlin, Frida and Mercier, Eric and Fremeaux-Bacchi, Veronique and Liszewski, M Kathryn and Atkinson, John P and Gris, Jean-Christophe and Blom, Anna}},
  issn         = {{1521-4141}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1617--1629}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{European Journal of Immunology}},
  title        = {{Analysis of genes coding for CD46, CD55 and C4b-binding protein in patients with idiopathic, recurrent, spontaneous pregnancy loss.}},
  url          = {{http://dx.doi.org/10.1002/eji.201243196}},
  doi          = {{10.1002/eji.201243196}},
  volume       = {{43}},
  year         = {{2013}},
}