Human Leukocyte Antigen May Predict Outcome of Primary Recurrent Spontaneous Abortion Treated with Paternal Lymphocyte Alloimmunization Therapy

  1. Takashi Kano1,†,
  2. Takahide Mori2,3,†,
  3. Masako Furudono1,
  4. Hironobu Ishikawa2,
  5. Hirohiko Watanabe2,
  6. Eri Kikkawa4,
  7. Takayuki Warita4,
  8. Makoto Onizuka4,
  9. Megumi Takahashi5,
  10. Yutaka Maeda6,
  11. Taeko Naruse5,
  12. Hidetoshi Inoko4,
  13. Akinori Kimura5

Article first published online: 5 SEP 2007

DOI: 10.1111/j.1600-0897.2007.00517.x

Issue

American Journal of Reproductive Immunology

American Journal of Reproductive Immunology

Volume 58, Issue 4, pages 383–387, October 2007

Additional Information

How to Cite

Kano, T., Mori, T., Furudono, M., Ishikawa, H., Watanabe, H., Kikkawa, E., Warita, T., Onizuka, M., Takahashi, M., Maeda, Y., Naruse, T., Inoko, H. and Kimura, A. (2007), Human Leukocyte Antigen May Predict Outcome of Primary Recurrent Spontaneous Abortion Treated with Paternal Lymphocyte Alloimmunization Therapy. American Journal of Reproductive Immunology, 58: 383–387. doi: 10.1111/j.1600-0897.2007.00517.x

Author Information

  1. 1

    Kano Medical Cooperation Clinic, Osaka, Japan

  2. 2

    Daigo Watanabe Clinic, Kyoto, Japan

  3. 3

    Medical Academia for Reproductive Regeneration, Kyoto, Japan

  4. 4

    Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan

  5. 5

    Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical ad Dental University, Tokyo, Japan

  6. 6

    FALCO biosystems, Ltd, Kyoto, Japan

  1. †

    Both authors contributed equally.

*Akinori Kimura, Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-Ku, Tokyo 101-0062, Japan. E-mail: akitis@mri.tmd.ac.jp

Publication History

  1. Issue published online: 5 SEP 2007
  2. Article first published online: 5 SEP 2007
  3. Submitted May 11, 2007; accepted June 26, 2007.

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Keywords:

  • Haplotype;
  • HLA-G;
  • paternal lymphocyte immunization;
  • recurrent spontaneous abortion

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-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, Pc = 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.

Conclusion

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

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