Human leucocyte antigen class Ib molecules in pregnancy success and early pregnancy loss

BACKGROUND: The human leucocyte antigen (HLA) class Ib molecules, HLA-E, -F and -G, are expressed at the materno-fetal interface. Because of the apparent immunoregulatory functions of these proteins, they may be involved in successful acceptance of the semi-allogenic fetus during pregnancy. METHODS: The literature on polymorphisms of the three genes, expression patterns of the proteins, and interactions with immune cell receptors have been evaluated to elucidate whether HLA-E, -F and -G are involved in the pathogenesis of some cases of recurrent miscarriages and unexplained infertility. RESULTS AND CONCLUSIONS: The HLA class Ib molecules seem to induce suppression of the maternal immune system, but are not necessarily fundamental factors for pregnancy success. However, evidence points towards low expression of these proteins, especially HLA-G, being associated with reduced fertility. To clarify the functions of HLA-E, -F and -G future studies need to link investigations of the polymorphisms in these genes to measurements of protein levels, and examine the role of these proteins in the complex interplay of immune cells and cytokines at the materno-fetal interface.