HLA Mismatches and Pregnancy: Research Review

HLA mismatches are assessed as part of the parental histocompatibility section of the IRMA report. Parental histocompatibility examines the impact of human leukocyte antigens (HLAs) on pregnancy.

HLAs are diverse proteins displayed on human cells like a barcode – unique for everyone. The immune system uses HLAs to differentiate “self” from “non-self.” Half of a developing embryo’s HLAs come from the father, and a certain amount of mismatch between parental HLAs is a good thing.

A mother’s immune system needs to develop tolerance to the embryo to maintain a healthy pregnancy. Part of this process lies in recognizing that the embryo is genetically unique. However, if the embryo inherits paternal HLAs that are too similar to the maternal HLAs, the immune system might not develop a strong tolerance. This test determines if there are enough mismatches between the maternal and paternal HLA Class II alleles.

Physiology

Human Leukocyte Antigen (HLA) genes [commonly referred to as the major histocompatibility complex (MHC) genes], are a cluster of genes present on the chromosome 6and are involved in antigen presentation to T cells to initiate an immune response.

In most cases, this immune reaction leads to the destruction of cells displaying “non-self” peptides.

There are two groups of HLA molecules, the class I includes HLA-A, -B, -C and the class II that includes HLA-DR, -DQ, and -DP.

HLA molecules play a key role in organ transplantation and are associated with many diseases including auto-immune disorders^1-2.

While a mismatch in Human Leukocyte Antigen (HLA) between a donor and a recipient in organ transplantation may lead to a graft rejection, most often due to the formation of antibodies³, a certain level of difference between the mother’s and father’s HLA alleles⁴ (inherited by the embryo and defined as a mismatch) is necessary to actively generate immune tolerance of the embryo⁵. Thus, couples with significant matched alleles for HLA genes may be more prone to infertility, repeated implantation failure, and recurrent pregnancy loss⁶.

Published clinical data

Although still controversial, the influence of HLA sharing on pregnancy outcome has been shown in clinical studies. Prospective studies of pregnancy outcome in an inbred population of European origins named “Hutterites” previously demonstrated increased fetal loss rates among couples with matching HLA^4-6.