Toward an understanding of allogeneic conflict in pregnancy and transplantation

Abstract

Pregnancy is recognized as a spontaneously acquired state of immunological tolerance by the mother to her semi-allogeneic fetus, but it is a major cause of allosensitization in candidates for organ transplantation. This sensitization, assessed by the presence of anti-HLA IgG, contributes to sex disparity in access to transplantation and increases the risk for rejection and graft loss. Understanding this dual tolerance/sensitization conundrum may lead to new strategies for equalizing access to transplantation among sexes and improving transplant outcomes in parous women. Here, we review the clinical evidence that pregnancy results in humoral sensitization and query whether T cell responses are sensitized. Furthermore, we summarize preclinical evidence on the effects of pregnancy on fetus-specific CD4+ conventional, regulatory, and CD8+ T cells, and humoral responses. We end with a discussion on the impact of the divergent effects that pregnancy has upon alloantigen re-encounter in the context of solid organ transplantation, and how these insights point to a therapeutic roadmap for controlling pregnancy-dependent allosensitization.

Construction of the systemic anticancer immune environment in tumour-bearing humanized mouse by using liposome-encapsulated anti-programmed death ligand 1 antibody-conjugated progesterone

“…During pregnancy, women develop an immune tolerance, which allows them to accept a semi-allogeneic fetus ( 34 ). In the mother, placental trophoblasts, which share the same characteristics as cancer cells, are confined to the uterus ( 6 , 7 ).…”

Donor-Specific Antibodies and Their Impact on Antibody-Mediated Rejection Post-Liver Transplantation: A Comprehensive Review

“…Preserving humoral immunity during pregnancy may inadvertently generate memory B cells and antibodies specific to the fetus, which could pose risks for subsequent organ transplants. However, despite these challenges, pregnancies can still occur, indicating robust mechanisms at the maternal-fetal interface [69]. These same mechanisms may alter the recipient's immune response to the transplanted liver.…”

The Molecular Mechanisms of HLA-G Regulatory Function on Immune Cells during Early Pregnancy

“…In the context of pregnancy, the embryo represents a unique semi-allograft [ 4 ] as it inherits half of its genes from the mother and the other half from the father. Remarkably, the maternal immune system does not reject the invading fetal EVTs during the endometrial invasion process.…”