Polyclonal Anti-D Antibodies Significantly Reduce the Rate of Miscarriages in Rh(D) positive Women with Recurrent Pregnancy loss.

Background Macrophages play a key role in all environmental conditions surrounding pregnancy. Coating of autologous red blood cells (RBCs) with polyclonal antibodies to Rh(D) antigen may result in an immunomodulation and improved outcome in Rh(D) positive women with recurrent pregnancy loss (RPL). Methods A total of 60 Rh(D) positive women (age 23 to 45 years) with a history of RPL and ineffective treatment with low molecular weight heparin (LMWH) and/or aspirin were included in this retrospective study. In addition to this treatment, Anti-D (300 μg) was given subcutaneously to each woman either prior to pregnancy and/or two times within 12 weeks of gestation. Results Treatment with Anti-D in non-responders to heparin/aspirin resulted in successful pregnancies in 67% of all cases. The remaining women had only aborts (23%) or did not become pregnant (10%). None of the treated women has developed anemia due to this treatment or any other significant adverse reaction. The rate of successful pregnancies does not appear to be influenced by the administration of: Anti-D prior to pregnancy, age, thrombophilia or previous alive births. Conclusion The improved outcome following the administration of Anti-D in women with RPL might be explained by immune modulations induced by different immune reactions including polarization of decidual macrophages. The results obtained in this study clearly indicate that Anti-D is safe and highly effective in treatment of Rh(D) positive women with RPL. However, further studies are required to support our results and to find out the optimal dose and timing of Anti-D administration.

[1]  J. Qiao,et al.  Role of Regulatory T Cells in Regulating Fetal-Maternal Immune Tolerance in Healthy Pregnancies and Reproductive Diseases , 2020, Frontiers in Immunology.

[2]  Liping Jin,et al.  Dynamic Function and Composition Changes of Immune Cells During Normal and Pathological Pregnancy at the Maternal-Fetal Interface , 2019, Front. Immunol..

[3]  H. Carp Immunotherapy for recurrent pregnancy loss. , 2019, Best practice & research. Clinical obstetrics & gynaecology.

[4]  Kang Chen,et al.  Role of Macrophages in Pregnancy and Related Complications , 2019, Archivum Immunologiae et Therapiae Experimentalis.

[5]  K. Baek,et al.  Pathogenetic factors involved in recurrent pregnancy loss from multiple aspects , 2019, Obstetrics & gynecology science.

[6]  K. O'Donoghue,et al.  A review of reproductive outcomes of women with two consecutive miscarriages and no living child , 2019, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology.

[7]  Yongli Yao,et al.  Macrophage Polarization in Physiological and Pathological Pregnancy , 2019, Front. Immunol..

[8]  H. Deshmukh,et al.  Immunological Basis for Recurrent Fetal Loss and Pregnancy Complications. , 2019, Annual review of pathology.

[9]  K. Shaw,et al.  Advances in the management of early pregnancy loss , 2018, Current opinion in obstetrics & gynecology.

[10]  H. Homer Modern management of recurrent miscarriage , 2018, The Australian & New Zealand journal of obstetrics & gynaecology.

[11]  Alison S Care,et al.  Regulatory T cells in embryo implantation and the immune response to pregnancy , 2018, The Journal of clinical investigation.

[12]  A. Liao,et al.  Modulatory effect of intravenous immunoglobulin on Th17/Treg cell balance in women with unexplained recurrent spontaneous abortion , 2018, American journal of reproductive immunology.

[13]  A. Zenclussen,et al.  Immune Cells at the Fetomaternal Interface: How the Microenvironment Modulates Immune Cells To Foster Fetal Development , 2018, The Journal of Immunology.

[14]  M. Juan,et al.  B Regulatory Cells: Players in Pregnancy and Early Life , 2018, International journal of molecular sciences.

[15]  Anthony J. Marren,et al.  Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice. , 2018, Australian journal of general practice.

[16]  N. Zhang,et al.  Distinct pattern of Th17/Treg cells in pregnant women with a history of unexplained recurrent spontaneous abortion. , 2018, Bioscience trends.

[17]  Weiping Li,et al.  An investigation of the relationship between recurrent spontaneous abortion and memory T follicular helper cells , 2017, American journal of reproductive immunology.

[18]  Yan Wang,et al.  Modulators of the Balance between M1 and M2 Macrophages during Pregnancy , 2017, Front. Immunol..

[19]  A. Salama Emerging drugs for immune thrombocytopenia (ITP) , 2017, Expert opinion on emerging drugs.

[20]  Surendra Sharma,et al.  Multiple Pregnancy Failures: An Immunological Paradigm , 2012, American journal of reproductive immunology.

[21]  A. Lazarus,et al.  Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn: what can we learn from rodent models? , 2009, Current opinion in hematology.

[22]  T. Dörner,et al.  Use of Heparin in Women With Early and Late Miscarriages With and Without Thrombophilia , 2009, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[23]  A. Lazarus,et al.  The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know? , 2008, Transfusion medicine reviews.

[24]  L. Regan,et al.  Recurrent miscarriage , 2006, The Lancet.

[25]  R. Mattar,et al.  Cytokines in recurrent pregnancy loss. , 2004, Journal of reproductive immunology.

[26]  J. Freedman,et al.  Anti-D initially stimulates an Fc-dependent leukocyte oxidative burst and subsequently suppresses erythrophagocytosis via interleukin-1 receptor antagonist. , 2003, Blood.

[27]  A. Lazarus,et al.  Mechanism of action of IVIG and anti-D in ITP. , 2003, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[28]  R. Kaufmann,et al.  Nonspecific immunity in pregnancy: monocyte surface Fcgamma receptor expression and function. , 1998, Journal of reproductive immunology.

[29]  Evaluation and treatment of recurrent pregnancy loss: a committee opinion. , 2012, Fertility and sterility.

[30]  F. Ringel,et al.  Polyclonal Anti-D Antibodies Significantly Reduce the Rate of Miscarriages in Rh(D) positive Women with Recurrent Pregnancy loss , 2022 .