title: Maternal-fetal HLA sharing and preeclampsia: variation in effects by seminal fluid exposure in a case-control study of nulliparous women in Iowa.
abstract: Whereas histocompatibility is critical for transplantation, HLA histoincompatibility is associated with successful pregnancy. Literature on HLA sharing and preeclampsia has been inconsistent; most studies focused on maternal-paternal rather than maternal-fetal sharing. This study examines whether maternal-fetal histocompatibility is associated with preeclampsia, and whether effects vary by semen exposure history. This case-control study of nulliparous women was designed to examine associations among HLA sharing, semen exposure, and preeclampsia. 258 preeclampsia cases and 182 normotensive controls met the eligibility criteria. HLA typing for mother and baby was performed for HLA-A, -B, -C, -DRB1, and -DQB1. We further restricted our study sample to 224 mother-baby pairs who had complete HLA typing for all five genes. Seminal fluid exposure indexes incorporated information on type of practice, frequency, contraceptive use (for vaginal exposure) and ingestion practices (for oral exposure). Multivariate models were adjusted for BMI and education. HLA-A matching, Class I matching, and combined Class I and II matching were associated with increased odds of preeclampsia. Among women with low semen exposure, effects of Class I matching were amplified (HLA-A matching, OR=6.27, 95%CI=1.04, 37.97; Class I matching, OR=4.49 per one-match increase, 95%CI=1.89, 14.50). With moderate to high semen exposure, Class II matching effects predominated (HLA-DQB1, OR=3.22, 95%CI=1.04, 9.99; Class II, OR=1.76 per one-match increase, 95%CI=1.05, 2.98; and total matches, OR=1.45 per one-match increase, 95%CI=1.02, 2.06). We found consistent evidence that maternal-fetal HLA sharing was associated with preeclampsia in a pattern influenced by prior vaginal exposure to paternal seminal fluid.
authors.affiliation: Department of Epidemiology, Brown University School of Public Health, Providence, RI 02912, USA. Electronic address: elizabeth_triche@brown.edu.
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Triche
authors.affiliation: Department of Emergency Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Injury Prevention Research Center, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Karisa K
authors.initials: KK
authors.lastname: Harland
authors.affiliation: Veterans Affairs Medical Center, Iowa City, IA 52246, USA; Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Field
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Rubenstein
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA.
authors.forename: Audrey F
authors.initials: AF
authors.lastname: Saftlas
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016022:Case-Control Studies; D003075:Coitus; D004781:Environmental Exposure / Q000706:statistics & numerical data; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology*; D006801:Humans; D007484:Iowa; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D010298:Parity; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000276:immunology*; D011247:Pregnancy; D012306:Risk; D012661:Semen / Q000276:immunology*; D012725:Sexual Behavior / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007519:Isoantigens
keywords: HLA sharing; Immunology; Maternal–fetal histocompatibility; Preeclampsia; Seminal fluid