A1 Refereed original research article in a scientific journal

HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage




AuthorsMeulernan T, van Beelen E, Kaaja RJ, van Lith JMM, Claas FHJ, Bloemenkamp KWM

PublisherELSEVIER IRELAND LTD

Publication year2016

JournalJournal of Reproductive Immunology

Journal name in sourceJOURNAL OF REPRODUCTIVE IMMUNOLOGY

Journal acronymJ REPROD IMMUNOL

Volume116

First page 28

Last page34

Number of pages7

ISSN0165-0378

DOIhttps://doi.org/10.1016/j.jri.2016.03.003


Abstract
HLA-C is the only polymorphic classical HLA I antigen expressed on trophoblast cells. It is known that higher incidence of C4d deposition on trophoblast cells is present in women with recurrent miscarriage. C4d is a footprint of antibody-mediated classical complement activation. Therefore, this study hypothesize that antibodies against HLA-C may play a role in the occurrence of unexplained consecutive recurrent miscarriage.Present case control study compared the incidence of HLA-C specific antibodies in 95 women with at least three consecutive miscarriages and 105 women with uneventful pregnancy. In the first trimester of the next pregnancy, presence and specificity of HLA antibodies were determined and their complement fixing ability. The incidence of HLA antibodies was compared with uni- and multivariate logistic regression models adjusting for possible confounders.Although in general a higher incidence of HLA antibodies was found in women with recurrent miscarriage 31.6% vs. in control subjects 9.5% (adjusted OR 4.3, 95% CI 2.0-9.5), the contribution of antibodies against HLA-C was significantly higher in women with recurrent miscarriage (9.5%) compared to women with uneventful pregnancy (1%) (adjusted OR 11.0, 95% CI 1.3-89.0). In contrast to the control group, HLA-C antibodies in the recurrent miscarriage group were more often able to bind complement.The higher incidence of antibodies specific for HLA-C in women with recurrent miscarriage suggests that HLA-C antibodies may be involved in the aetiology of unexplained consecutive recurrent miscarriage. (C) 2016 Elsevier Ireland Ltd. All rights reserved.



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