The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth.
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.
Nielsen
Henriette Svarre
HS
The Fertility Clinic, University Hospital Copenhagen, Rigshospitalet, Fertility Clinic 4071, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. henriette.svarre.nielsen@rh.regionh.dk
Witvliet
Marian D
MD
Steffensen
Rudi
R
Haasnoot
Geert W
GW
Goulmy
Els
E
Christiansen
Ole Bjarne
OB
Claas
Frans
F
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
D006680:HLA Antigens; D007518:Isoantibodies