人类白细胞抗原可能预测经父方淋巴细胞同种免疫疗法治疗的原发性复发性自然流产的结局。

Human leukocyte antigen may predict outcome of primary recurrent spontaneous abortion treated with paternal lymphocyte alloimmunization therapy.

作者信息

Kano Takashi, Mori Takahide, Furudono Masako, Ishikawa Hironobu, Watanabe Hirohiko, Kikkawa Eri, Warita Takayuki, Onizuka Makoto, Takahashi Megumi, Maeda Yutaka, Naruse Taeko, Inoko Hidetoshi, Kimura Akinori

机构信息

Kano Medical Cooperation Clinic, Osaka, Japan.

出版信息

Am J Reprod Immunol. 2007 Oct;58(4):383-7. doi: 10.1111/j.1600-0897.2007.00517.x.

DOI:10.1111/j.1600-0897.2007.00517.x

PMID:17845209

Abstract

PROBLEM

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.

METHOD OF STUDY

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-G010401, A2402, B5201, and DRB11502 were significantly increased in the aborted cases than those in the succeeded cases or controls. Of note, HLA-G010401 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-G010401 could predict the abortion after PLAT with sensitivity and specificity of 100% and 48.1%, respectively.

CONCLUSION

Human leukocyte antigen testing may be useful for predicting effectiveness of PLAT in RSA.

摘要

问题

复发性自然流产（RSA）的定义是在其他方面健康的夫妇中至少连续发生三次流产。父方淋巴细胞免疫疗法（PLAT）在某些情况下是治疗RSA的有效疗法，但尚无关于PLAT有效性的预测标志物。

研究方法

以42例接受PLAT治疗的原发性RSA连续病例和23例对照为研究对象。通过测序分型研究人类白细胞抗原（HLA）-E、HLA-G、HLA-A、HLA-B、HLA-C和HLA-DRB1的多态性。还研究了HLA-G的启动子多态性和外显子8中的14bp插入/缺失多态性。

结果

38例RSA患者在PLAT治疗后1年内怀孕。其中，27例成功分娩（PLAT治疗成功病例），而11例再次流产，流产胎儿未检测到染色体异常（PLAT治疗流产病例）。流产病例中HLA-G010401、A2402、B5201和DRB11502的频率显著高于成功病例或对照。值得注意的是，所有流产病例中均发现HLA-G010401，而成功病例中该基因的检出率为51.9%（优势比=21.4，P = 0.006，P(c)=0.03），HLA-G010401的存在可预测PLAT治疗后的流产，敏感性和特异性分别为100%和48.1%。