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

Joonho Lee, Roberto Romero, Yi Xu, Jezid Miranda, Wonsuk Yoo, Piya Chaemsaithong, Juan Pedro Kusanovic, Tinnakorn Chaiworapongsa, Adi L. Tarca, Steven J. Korzeniewski, Sonia S. Hassan, Nandor Gabor Than, Bo Hyun Yoon, Chong Jai Kim

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)162-175
Number of pages14
JournalAmerican Journal of Reproductive Immunology
Volume70
Issue number2
DOIs
Publication statusPublished - 2013 Aug 1

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Second Pregnancy Trimester
HLA Antigens
Mothers
Antibodies
Isoantibodies
Pregnancy
Pregnant Women
Gravidity
Histocompatibility Antigens Class I
Premature Obstetric Labor
Maternal Age
Parity
Gestational Age
Longitudinal Studies
Case-Control Studies
Epitopes
Flow Cytometry
Fetus
Genotype

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Lee, Joonho ; Romero, Roberto ; Xu, Yi ; Miranda, Jezid ; Yoo, Wonsuk ; Chaemsaithong, Piya ; Kusanovic, Juan Pedro ; Chaiworapongsa, Tinnakorn ; Tarca, Adi L. ; Korzeniewski, Steven J. ; Hassan, Sonia S. ; Than, Nandor Gabor ; Yoon, Bo Hyun ; Kim, Chong Jai. / 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. In: American Journal of Reproductive Immunology. 2013 ; Vol. 70, No. 2. pp. 162-175.
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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 = "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.",
author = "Joonho Lee and Roberto Romero and Yi Xu and Jezid Miranda and Wonsuk Yoo and Piya Chaemsaithong and Kusanovic, {Juan Pedro} and Tinnakorn Chaiworapongsa and Tarca, {Adi L.} and Korzeniewski, {Steven J.} and Hassan, {Sonia S.} and Than, {Nandor Gabor} and Yoon, {Bo Hyun} and Kim, {Chong Jai}",
year = "2013",
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doi = "10.1111/aji.12141",
language = "English",
volume = "70",
pages = "162--175",
journal = "American Journal of Reproductive Immunology and Microbiology",
issn = "1046-7408",
publisher = "Wiley-Blackwell",
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Lee, J, Romero, R, Xu, Y, Miranda, J, Yoo, W, Chaemsaithong, P, Kusanovic, JP, Chaiworapongsa, T, Tarca, AL, Korzeniewski, SJ, Hassan, SS, Than, NG, Yoon, BH & Kim, CJ 2013, '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', American Journal of Reproductive Immunology, vol. 70, no. 2, pp. 162-175. https://doi.org/10.1111/aji.12141

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. / Lee, Joonho; Romero, Roberto; Xu, Yi; Miranda, Jezid; Yoo, Wonsuk; Chaemsaithong, Piya; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Korzeniewski, Steven J.; Hassan, Sonia S.; Than, Nandor Gabor; Yoon, Bo Hyun; Kim, Chong Jai.

In: American Journal of Reproductive Immunology, Vol. 70, No. 2, 01.08.2013, p. 162-175.

Research output: Contribution to journalArticle

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 - 2013/8/1

Y1 - 2013/8/1

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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