Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges

Abstract

Due to the expression of paternal antigens by the embryo, pregnancy is considered as a semi-allograft and so immunological dysregulation is considered as one of the important causes in repeated implantation failure (RIF) and recurrent pregnancy loss (RPL). It has been revealed that lymphocytes immunotherapy (LIT) could be an appropriate approach to prevent pregnancy loss in such patients. Various mechanisms have been suggested for effectiveness of LIT such as enhancing expression of anti-paternal cytotoxic antibodies (APCA), progesterone-induced blocking factor (PIBF), anti-idiotypic antibodies (Ab2), and mixed lymphocyte reaction blocking antibodies (MLR-Bf), as well as reduction in the T helper 1/T helper 2 ratio and deviation in the pattern of cytokines production. However, there are controversial results about the beneficial effect of LIT treatment in RIF and RPL patients. In the current study, we reviewed findings of LIT in RIF and RPL patients with a focus on possible mechanisms of alloimmunization in preserving pregnancy. Besides, we highlighted possible reasons for mixed results about the effectiveness of LIT and way of solving the problem. Also, we proposed potential laboratory and clinical criteria to recruit patients for LIT.

Characterisation of serum progesterone and progesterone-induced blocking factor (PIBF) levels across trimesters in healthy pregnant women

“…PIBF is recognised as a potential therapeutic agent or marker in lymphocyte immunotherapy for the reduction of miscarriage risk. Given that current research has pointed towards an active recognition and response to fetal antigens by the maternal immune system during pregnancy 44 , and the concomitant deviation of the maternal immune system towards that of tolerance as evidenced by the key role of regulatory T cells in healthy pregnancies 45 , lymphocyte immunotherapy may aid in supporting the development of immunological tolerance to the semi-allogeneic fetus. This therapy may be instrumental in treating recurrent spontaneous abortions, given that Th1 cytokines and NK cell over-activity are said to be major alloimmune drivers of this condition 46 .…”

Comparison of the effects of Duphaston and Cetrotide on oocyte and embryo quality in women undergoing ICSI: A cross-sectional study

“…About 8-12% of reproductive-aged couples suffer from infertility worldwide (1). Over the last decade, assisted reproductive technology (ART) have drawn considerable attention to overcome the problem of infertility (2). Interestingly, the premature luteinizing hormone (LH) surge is one of the main causes for ART cycle cancellation.…”

CXCL16/CXCR6 interaction promotes endometrial decidualization via the PI3K/AKT pathway

“…On one hand, decidual cells surrounding the early conceptus have been shown to epigenetically silence key chemokine genes, thus protecting the allogeneic foetus from attack of cytotoxic lymphocytes (Nancy et al 2012). On the other hand, chemokines (such as interleukin 12) could also induce the proinflammatory microenvironment and underpin endometrial receptivity and early implantation in pregnancy (Hajipour et al 2018). Therefore, the decidual cells could adapt dynamically and tailor their chemokine secretome to accommodate the various stages of the implantation process (Guzeloglu-Kayisli et al 2009).…”