Session Speaker

The Human Leukocyte Antigen-G Molecule: A Novel Marker and Therapeutic Tool In Human Transplantation
Diego Delgado
Canada

Human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex class I molecule primarily expressed by the trophoblast cells of the placenta. HLA-G is an important natural tolerogenic molecule in the context of fetal-maternal tolerance. HLA-G has been reported to have a protective effect towards the fetus by inhibiting the cytotoxic activity of T lymphocytes and NK cells. This phenomenon is widely believed to be one explanation why mothers are able to accommodate their fetus even though they do not share the same genetic information. However, because of HLA-G’s broad inhibitory function, capable of targeting multiple immune cell subsets, much effort has been put into determining whether HLA-G is pathologically relevant, and whether it can be used as a diagnosis tool or as a therapeutic tool and/or target.

In transplantation, HLA-G expression significantly correlates with hepatic, renal and lung graft rejection. We have found that HLA-G is expressed in the myocardium and serum of heart transplant patients. Patients expressing HLA-G had fewer episodes of graft rejection and lower incidence of graft vasculolopathy. These results suggest that HLA-G expression may diminish the host immune response thereby reducing rejection and coronary disease in the graft.

We are focused on the endothelium as a potential target for pharmacologic interventions. We found that cultured endothelial cells are capable of expresing HLA-G. The fact that the endothelium is able to express HLA-G raises the possibility that HLA-G in the graft may be protective against graft vasculopathy. We recently found that heart transplant patients treated with the antiproliferative agent Everolimus have significantly higher serum HLA-G levels than patients on other immunosuppressive agents.

The use of recombinant engineered HLA-G proteins is a novel therapeutic option to induce tolerance in patients post transplantation.

Induction of donor-specific tolerance is a major goal in organ transplantation. New developments and investigations in this area may change the future of transplantation. Therefore, investigations in HLA-G may contribute to a better understanding of the tolerance process.