TY - JOUR
T1 - 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
AU - Lee, Joonho
AU - Romero, Roberto
AU - Xu, Yi
AU - Miranda, Jezid
AU - Yoo, Wonsuk
AU - Chaemsaithong, Piya
AU - Kusanovic, Juan Pedro
AU - Chaiworapongsa, Tinnakorn
AU - Tarca, Adi L.
AU - Korzeniewski, Steven J.
AU - Hassan, Sonia S.
AU - Than, Nandor Gabor
AU - Yoon, Bo Hyun
AU - Kim, Chong Jai
PY - 2013/8
Y1 - 2013/8
N2 - Problem: 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 of study: 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. Conclusion: 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.
AB - Problem: 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 of study: 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. Conclusion: 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.
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U2 - 10.1111/aji.12141
DO - 10.1111/aji.12141
M3 - Article
C2 - 23841577
AN - SCOPUS:84880286322
SN - 1046-7408
VL - 70
SP - 162
EP - 175
JO - American Journal of Reproductive Immunology
JF - American Journal of Reproductive Immunology
IS - 2
ER -
