title: HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage.
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.
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands. Electronic address: t.meuleman@lumc.nl.
authors.forename: T
authors.initials: T
authors.lastname: Meuleman
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van Beelen
authors.affiliation: Department of Obstetrics and Gynaecology, Turku University, 20610 Turku, Finland.
authors.forename: R J
authors.initials: RJ
authors.lastname: Kaaja
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: J M M
authors.initials: JM
authors.lastname: van Lith
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands.
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
authors.affiliation: Department of Obstetrics, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands; Department of Obstetrics, Wilhelmina Children Hospital Birth Centre, Utrecht University Medical Centre, 3508 AB Utrecht, The Netherlands.
authors.forename: K W M
authors.initials: KW
authors.lastname: Bloemenkamp
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology*; D000328:Adult; D000906:Antibodies / Q000378:metabolism; D000920:Antibody-Dependent Cell Cytotoxicity; D016022:Case-Control Studies; D003167:Complement Activation; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D015236:HLA-C Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011485:Protein Binding; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D000906:Antibodies; D015236:HLA-C Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: HLA antibodies; Humoral rejection; Immunology; Pregnancy; Recurrent miscarriage