Pathogenesis, diagnosis, and treatment of recurrent spontaneous abortion with immune type

Abstract

Recurrent spontaneous abortion (RSA), defined as three or more consecutive pregnancy losses before 20 weeks of gestation, is difficult to treat in the clinical setting. It affects 1%–5% of women of reproductive age. In the investigations of immunopathogenesis, diagnosis, and treatment of RSA since the late 1980s, it was found that RSA was associated with abnormal maternal local or systemic immune response. The pathogenesis of autoimmune RSA was mainly associated with antiphospholipid antibody (APA), while that of alloimmune RSA was due to the disturbance of maternofetal immunological tolerance. Systemic etiological screening process and diagnosis systems of RSA with immune type were developed, and anticardiolipin (ACL or ACA) + anti-β2-GP1 antibody combining multiple assays for effective diagnosis of RSA with autoimmune type was first established. According to the dynamic monitoring of clinical parameters before and during gestation, low-dose, short-course, and individual immunosuppressive therapy and lymphocyte immunotherapy for RSA with immune type were carried out. The outcomes of the offsprings of patients with RSA were followed up, and the safety and validity of the therapies were confirmed. The research achievement leads to great progress in the diagnosis and treatment of RSA in China.

Keywords

spontaneous abortion, recurrent / autoimmune / alloimmune / pathogenesis / diagnosis / immunotherapy

References

[1] LinQ D, ZhouH C, ZhaoA M, YanJ H, WuY F, TangX W, ZhuL H, DiW, KangJ F, WangY, ChenS L, JiangB Z, ChenM S. The relationship between recurrent spontaneous abortion and autoantibodies. Zhonghua Fu Chan Ke Za Zhi, 1993, 28(11): 674-677 (in Chinese)

[2] ZhaoA M, LinQ D, ZhouH C, JiangL L, YanJ H, WuY F. Immunohistochemical study on the decidua vessels in recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi, 1997, 32(11): 674-677 (in Chinese)

[3] TanY Y, LinQ D, ZhaoA M. The relationship between recurrent spontaneous abortion and anticardiolipin antibody. Zhongguo Mian Yi Xue Za Zhi, 1999, 15(12): 545-546

[4] WangX P, MaZ H, LinQ D. Inherited thrombophilia in recurrent spontaneous abortion among Chinese women. Int J Gynaecol Obstet, 2006, 92(3): 264-265

[5] WangX P, LinQ D, MaZ W, ZhaoA M. C677T and A1298C mutation of the methylenetetrahydrofolate reductase gene in unexplained recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi, 2004, 39(4): 238-241 (in Chinese)

[6] WangX P, MaZ H, HongY, ZhaoA M, QiuL H, LuP H, LinQ D. The skewed TCR-BV repertoire displayed at the maternal-fetal interface of women with unexplained pregnancy loss. Am J Reprod Immunol, 2005, 54(2): 84-95

[7] WangX P, LinQ D, MaZ W, HongY, ZhaoA M, DiW, LuP H. Association of the A/G polymorphism at position 49 in exon 1 of CTLA-4 with the susceptibility to unexplained recurrent spontaneous abortion in the Chinese population. Am J Reprod Immunol, 2005, 53(2): 100-105

[8] WangX P, LinQ D, MaZ W, HongY, ZhaoA M, DiW, LuP H. A/G polymorphism at position 49 in exon 1 of CTLA-4 gene in Chinese women with unexplained recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi, 2006, 41(3): 155-158 (in Chinese)

[9] QiuL H, LinQ D. Study on the relationship between regulatory T cells and unexplained recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi, 2004, 39(12): 816-818 (in Chinese)

[10] YangH, QiuL H, ChenG J, YeZ, LüC J, LinQ D. Proportional change of CD4+CD25+ regulatory T cells in unexplained recurrent spontaneous abortion patients. Fertil Steril, 2008, 89(3): 656-661

[11] YangH, QiuL, DiW, ZhaoA, ChenG, HuK, LinQ. Proportional change of CD4+CD25+ regulatory T cells after lymphocyte therapy in unexplained recurrent spontaneous abortion patients. Fertil Steril, 2009, 92(1): 301-305

[12] QiuL H, LinQ D, ShenZ Y, LuP H, LiD Z, HongY. The influence of active immunotherapy on serum T helper cell type 1 and 2 cytokines balance in unexplained habitual abortion patients. Zhonghua Fu Chan Ke Za Zhi, 2002, 37(6): 368-369 (in Chinese)

[13] QiuL H, LinQ D, HongY, LiD Z, DingC W. Study on changes of serum T helper cell type 1 and 2 cytokines after active immunotherapy in women with unexplained habitual abortion. Zhonghua Fu Chan Ke Za Zhi, 2001, 36(7): 408-410 (in Chinese)

[14] WangW J, HaoC F, Yi-Lin, YinG J, BaoS H, QiuL H, LinQ D. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol, 2010, 84(2): 164-170

[15] HongY, LinQD, WangXP. The relationship between the expression of KIR’ repertoire in decidua and unexplained spontaneous abortion. Xiandai Fuchanke Jinzhan, 2005, 14(3): 214-217 (in Chinese)

[16] LinY, ChenY, ZengY, WangT, ZengS. Lymphocyte phenotyping and NK cell activity analysis in pregnant NOD/SCID mice. J Reprod Immunol, 2005, 68(1-2): 39-51

[17] LinY, LiangZ H, ChenY J, ZengY Y. TLR3-involved modulation of pregnancy tolerance in double-stranded RNA-stimulated NOD/SCID mice. J Immunol, 2006, 176(7): 4147-4154

[18] JinY, LinQ D, WangX P, XiaoY S, LüC J, DingC W. Expression of TSP1, CD36, CD47 and cytokine secretion on macrophage of women with unexplained recurrent spontaneous abortion. Xiandai Fu Chan Ke Jin Zhan, 2006, 15(12): 926-929 (in Chinese)

[19] WangX P, LinQ D, LuP H, MaZ W, ZhaoA M. Association of HLA-DQB1 coding region with unexplained recurrent spontaneous abortion. Chin Med J (Engl), 2004, 117(4): 492-497

[20] LinQ D. Recurrent spontaneous abortion and habitual abortion caused by immune factors. Zhonghua Fu Chan Ke Za Zhi, 2000, 35(12): 760 (in Chinese)

[21] LinQ D, JinY. How to standardize the etiology screening and theatment of recurrent spontaneous abortion? Shiyong Fu Chan Ke Za Zhi, 2005, 21(2): 66-68 (in Chinese)

[22] LinQ D, ZhouH C, ZhaoA M, YanJ H, WuY F, TangX W, ZhuL H, DiW, KangJ F, WangY, ChenS L, JiangB Z, ChenM S. Immunological diagnosis and treatment of unexplained recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi, 1993, 28(3): 143 (in Chinese)

[23] BaoS H, WangX P, LinQ D, DiW, XuL, DingC W. The investigation on the value of repeat and combination test of ACA and anti-β2-GPI antibody in women with recurrent spontaneous abortion. Am J Reprod Immunol, 2008, 60(4): 372-378

[24] XuL, LinQ D, WangX P, ZhaoA M. The application of individualized immune-s uppression and anticoagulant in therapy of RSA with ACA. Zhongguo Shi Yong Fu Ke Yu Chan Ke Za Zhi, 2006, 22(9): 666-668 (in Chinese)

[25] ChenQ H, LinQ D, ZhaoA M, ZhouY, TangX W, YanJ H. Following up the offspring of the unexplained recurrent spontaneous abortion women receiving active immunotherapy. Zhonghua Fu Chan Ke Za Zhi, 1997, 32(1): 44-45 (in Chinese)

[26] ZhengX G, HuangL P, LinQ D, WangX P, LinJ H, DiW, KongX M. Following up the offspring of the recurrent spontaneous abortion women with anticardiolipin antibody receiving the individual therapy with immune-suppression and anticoagulant therapy. Zhongguo Shi Yong Fu Ke Yu Chan Ke Za Zhi, 2008, 24(3): 192-194 (in Chinese)

Acknowledgements

The study was supported by the National Natural Science Foundation of China (Grant Nos. 30730087, 30530740, 389073, 39470722, 39870666, 39870775, 30471822, and 30672231).

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg