Biologic mechanisms and clinical consequences of pregnancy alloimmunization.

Alloimmunization occurs during pregnancy when tissue antigens derived from the fetus and/or placenta prime maternal immune cells to divide and differentiate. For many women, the result of pregnancy alloimmunization is the formation of anti-HLA antibody that can endure for decades and preclude transplantation by limiting donor compatibility. Pregnancy alloimmunization may also generate memory B cells that can rapidly produce anti-HLA antibody after transplantation as well as pathogenic memory T cells, which pose a threat to graft survival. However, emerging data suggest that pregnancy also programs the differentiation of anergic, dysfunctional, and regulatory T cell populations, which may not mediate accelerated graft rejection. Hence, some of the immune mechanisms responsible for maternal immunologic tolerance of the fetus may persist into postpartum life and affect the response to an allograft. This review discusses these emerging data as well as the persistent knowledge gaps that affect women at multiple stages of their transplant care.