Human leukocyte antigen may predict outcome of primary recurrent spontaneous abortion treated with paternal lymphocyte alloimmunization therapy.
OBJECTIVE
Recurrent spontaneous abortion (RSA) is defined by at least three consecutive abortions in otherwise healthy couples. Paternal lymphocyte alloimmunization therapy (PLAT) is an effective therapy for RSA in some cases, but there are no predictive markers about the effectiveness of PLAT.


METHODS
Forty-two consecutive cases with primary RSA treated by PLAT and 23 controls were the subjects. Polymorphisms of human leukocyte antigen (HLA)-E, HLA-G, HLA-A, HLA-B, HLA-C and HLA-DRB1 were investigated by sequenced based typing. Promoter polymorphism and a 14 bp ins/del polymorphism in exon 8 were also investigated for HLA-G.


RESULTS
Thirty-eight RSA wives became pregnant within 1 year after PLAT. Among them, 27 obtained babies (succeeded PLAT cases), while 11 again aborted with no detectable chromosomal abnormalities in the aborted fetuses (aborted PLAT cases). The frequencies of HLA-G*010401, A*2402, B*5201, and DRB1*1502 were significantly increased in the aborted cases than those in the succeeded cases or controls. Of note, HLA-G*010401 was found in all aborted cases whereas it was found in 51.9% of succeeded cases (odds ratio = 21.4, P = 0.006, P(c) = 0.03), and the presence of HLA-G*010401 could predict the abortion after PLAT with sensitivity and specificity of 100% and 48.1%, respectively.


CONCLUSIONS
Human leukocyte antigen testing may be useful for predicting effectiveness of PLAT in RSA.
Kano
Takashi
T
Kano Medical Cooperation Clinic, Osaka, Japan.
Mori
Takahide
T
Furudono
Masako
M
Ishikawa
Hironobu
H
Watanabe
Hirohiko
H
Kikkawa
Eri
E
Warita
Takayuki
T
Onizuka
Makoto
M
Takahashi
Megumi
M
Maeda
Yutaka
Y
Naruse
Taeko
T
Inoko
Hidetoshi
H
Kimura
Akinori
A
D000026:Abortion, Habitual / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D059951:HLA-G Antigens; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D050498:Live Birth; D017710:Lymphocyte Transfusion; D018579:Patient Selection; D011110:Polymorphism, Genetic; D011247:Pregnancy; D016896:Treatment Outcome
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I