title: Detection of anti-HLA antibodies in maternal blood in the second trimester to identify patients at risk of antibody-mediated maternal anti-fetal rejection and spontaneous preterm delivery.
abstract: OBJECTIVE
  Maternal anti-fetal rejection is a mechanism of disease in spontaneous preterm labor. The objective of this study was to determine whether the presence of human leukocyte antigen (HLA) panel-reactive antibodies (PRA) during the second trimester increases the risk of spontaneous preterm delivery.
  
  
  METHODS
  This longitudinal case-control study included pregnant women with spontaneous preterm deliveries (n = 310) and control patients with normal term pregnancies (n = 620), matched for maternal age and gravidity. Maternal plasma samples obtained at 14-16, 16-20, 20-24, and 24-28 weeks of gestation were analyzed for HLA class I and class II PRA positivity using flow cytometry. The fetal HLA genotype and maternal HLA alloantibody epitope were determined for a subset of patients with positive HLA PRA.
  
  
  RESULTS
  (i) Patients with spontaneous preterm delivery were more likely to exhibit HLA class I (adjusted OR = 2.54, P < 0.0001) and class II (adjusted OR = 1.98, P = 0.002) PRA positivity than those delivering at term; (ii) HLA class I PRA positivity for patients with spontaneous preterm delivery between 28 and 34 weeks (adjusted OR = 2.88; P = 0.001) and after 34 weeks of gestation (adjusted OR = 2.53; P < 0.0001) was higher than for those delivering at term; (iii) HLA class II PRA positivity for patients with spontaneous preterm delivery after 34 weeks of gestation was higher than for those delivering at term (adjusted OR = 2.04; P = 0.002); (iv) multiparous women were at a higher risk for HLA class I PRA positivity than nulliparous women (adjusted OR = 0.097, P < 0.0001 for nulliparity); (v) nulliparous women had a higher rate of HLA class I PRA positivity with advancing gestational age (P = 0.001); and (vi) 78% of women whose fetuses were genotyped had alloantibodies specific against fetal HLA class I antigens.
  
  
  CONCLUSIONS
  Pregnant women with positive HLA class I or class II PRA during the second trimester are at an increased risk of spontaneous preterm delivery due to antibody-mediated maternal anti-fetal rejection.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA.
authors.forename: JoonHo
authors.initials: J
authors.lastname: Lee
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Jezid
authors.initials: J
authors.lastname: Miranda
authors.forename: Wonsuk
authors.initials: W
authors.lastname: Yoo
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Kusanovic
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Korzeniewski
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Yoon
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005333:Fetus / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000097:blood / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood*; D047928:Premature Birth / Q000276:immunology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies
keywords: Flow cytometry; preterm birth; rejection; transplantation