title: The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth.
abstract: Anti-paternal HLA-antibodies are considered a harmless phenomenon during most pregnancies, whereas their role in recurrent miscarriage (RM) patients is disputed. In contrast to primary RM, patients with secondary RM have carried a fetus to term pregnancy prior to a series of miscarriages, which increases the chance that allogeneic fetal cells appear in the maternal circulation. This study investigates the frequency of HLA-antibodies in secondary RM, primary RM patients and parous controls and analyzes whether the presence of HLA-antibodies in early pregnancy is associated with pregnancy outcome. Sera from women with secondary RM (n=56), primary RM (n=13) and parous controls (n=24) were tested for HLA-antibodies using an ELISA assay and complement dependent cytotoxicity. Samples were taken at gestational week 4-5 in 62 (90%) of the patients. HLA-antibodies were significantly more frequent in secondary RM patients with a boy prior to the miscarriages (62%) compared to secondary RM patients with a firstborn girl (29%, p=0.03), primary RM patients (23%, p=0.02) and parous controls (25%, p=0.005). Forty-one percent of HLA-antibody positive pregnant RM patients had a live birth compared to 76% of HLA-antibody negative RM patients, p=0.006 (adjusted OR: 0.22 (0.07-0.68), p=0.008). In conclusion, HLA-antibodies are significantly more frequent in secondary RM patients with a firstborn boy than in other RM patients and controls. The presence of these antibodies in early pregnancy is associated with a reduced chance of a live birth. Further exploring this association may increase our understanding of maternal acceptance of the fetal allograft.
authors.affiliation: The Fertility Clinic, University Hospital Copenhagen, Rigshospitalet, Fertility Clinic 4071, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. henriette.svarre.nielsen@rh.regionh.dk
authors.forename: Henriette Svarre
authors.initials: HS
authors.lastname: Nielsen
authors.forename: Marian D
authors.initials: MD
authors.lastname: Witvliet
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.forename: Geert W
authors.initials: GW
authors.lastname: Haasnoot
authors.forename: Els
authors.initials: E
authors.lastname: Goulmy
authors.forename: Ole Bjarne
authors.initials: OB
authors.lastname: Christiansen
authors.forename: Frans
authors.initials: F
authors.lastname: Claas
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics / Q000276:immunology*; D000328:Adult; D000918:Antibody Specificity; D003601:Cytotoxicity Tests, Immunologic; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D054502:Histocompatibility, Maternal-Fetal; D006801:Humans; D007108:Immune Tolerance; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D050498:Live Birth; D016017:Odds Ratio; D011247:Pregnancy / Q000276:immunology*; D011256:Pregnancy Outcome; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies