Lymphocytes Immunotherapy for Preserving Pregnancy
A Ray of hope for Mothers –To-Be
❖ Lymphocyte immunotherapy (LIT) is a cost-effective, safe, and useful approach, with a proper dose of fresh lymphocytes inducing intradermally before and during pregnancy.
❖ LIT induces the production of anti-paternal cytotoxic antibodies (APCAs), mixed lymphocyte reaction blocking antibodies (MLR- Babs or MLR-BF), and anti-idiotypic antibodies (Ab2) that can cover paternal human leukocyte antigen (HLA) in the surface of the fetus and thereby prevent from maternal natural killer (NK) and T cells attacking.
❖ LIT significantly reduces T helper (Th-1 and Th-17) and increases Th2 and regulatory T (Treg) cells levels and consequently causes an increase in cytokines produced by Th2 and Treg such as interleukin (IL) – 10, – 4 and transforming growth factor beta (TGFß) which act in favor of a successful gestation; while decreases Th1 and Th17 secreted cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor- alpha (TNF-a) that act against pregnancy.
❖ Overall, cell therapy mechanisms of action are inducing the production of cytokines, blocking antibodies and growth factors, the proliferation of B10 cells, reducing the activity of NK cells, increasingTh2 and Treg cells, and decreasing Th1 and Th17 cells.
❖ Immunotherapy is a treatment for unexplained pregnancy loss or IVF failure. A recent study reported from eighteen randomized, placebo-controlled trials that Immunotherapy performed before and during pregnancy had dramatically improved the live birth rate in women with unexplained pregnancy loss or IVF failure. The success rate of treatment group was significantly higher.
❖ Immunotherapy given before and during pregnancy is superior to given only before pregnancy, and the lower doses per treatment achieved a better outcome.
❖ Although cell therapy is a promising approach, can be an effective strategy as it provides an interactive, dynamic, specific, and individualized treatment.
Overall, LIT modulates the mother’s immune system to protect the fetus and make the pregnancy prosperous.
Figure: Possible mechanism by which leukocyte immunotherapy (LIT) enhances pregnancy rate in women with recurrent pregnancy loss. (Hajipour et al., 2018).
Some of the country listed below with reference:
- Pandey MK, Thakur S, Agrawal S. Lymphocyte immunotherapy and its probable mechanism in the maintenance of pregnancy in women with recurrent spontaneous abortion. Arch Gynecol Obstet 2004; 269(3): 161-72.
- Kumar A. 2014. Immunomodulation in Recurrent Miscarriage. The Journal of Obstetrics and Gynecology of India. 2014, 64(3):165–168
- Sibylle Wegener et al., Immunotherapy with Paternal Lymphocytes for Recurrent Miscarriages and Unsuccessful in vitro Fertilization Treatment. Transfus Med Hemother 2006;33:501–507
- Liu Z, Xu H, Kang X, Wang T, He L, Zhao A. Allogenic lymphocyte immunotherapy for unexplained recurrent spontaneous abortion: a meta-analysis. Am J Reprod Immunol 2016
- Yan-Jiao Hua, et al. 2016. Lymphocyte immunotherapy for recurrent spontaneous abortion in patients with negative blocking antibody. Int J Clin Exp Med 2016;9(6):9856-9867
- Wu et al. 2014. Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy Reproductive Biology and Endocrinology 2014, 12:74
- Ho HN, et al. 1991. Immunotherapy for recurrent spontaneous abortions in a Chinese population. Am J Reprod Immunol 1991; 25:10–15.
- Mitra Rafiee et al. 2015. Altered Th17/Treg Ratio in Recurrent Miscarriage after Treatment with Paternal Lymphocytes and Vitamin D3: a Double-Blind Placebo-Controlled Study. Rafiee M, et al. Iran J Immunol. 2015; 12(4):252-262.
- Bansal A.S. et al. 2012. The basis and value of currently used immunomodulatory therapies in recurrent miscarriage. Journal of Reproductive Immunology 93 (2012) 41– 51
- Kim D. Ly et al. 2010. Evidence-Based Management of Infertile Couples with Repeated Implantation Failure Following IVF. Current Women’s Health Reviews, 2010, 6, 200-218
- Hanna Motak-Pochrzęst et al. 2015. Polish experiences with paternal lymphocyte immunization in women with recurrent miscarriages. Neuroendocrinology Letters Volume 36 No. 6 2015
- Mette Dahl et al. 2012. Human leucocyte antigen class Ib molecules in pregnancy success and early pregnancy loss. Human Reproduction Update, Vol.18, No.1 pp. 92–109
- Hiroshi Fujiwara et al. 2010. Possible Contribution of Circulating Blood Cells to Embryo Implantation. Indian J Physiol Pharmacol 54 (5) 2010 ; 51-59
- Check J.H et al. 2005. Lymphocyte immunotherapy can improve pregnancy outcome following embryo transfer (ET) in patients failing to conceive after two previous ET. Clin.Exp.Obst &Gyn-ISSN:0390-6663, XXXII, n 1, 2005.
- Alan E. Beer Medical Center for Reproductive Immunology, USA
- Antonis Makrigiannakis et al. 2015. Repeated implantation failure: a new potential treatment option. Department of Obstetrics and Gynecology, Medical School, University of Crete, Heraklion, Greece
- The Fertility & Gynecology Academy