Relevance of Human Leukocyte Antigen Class C Donor-Specific Antibodies in Kidney Transplant

Kidney transplant is well known to be the best possible therapy for patients with end-stage kidney failure; however, allograft rejection remains a major obstacle despite the advent of modern immunosuppression regimens. Despite the well-established role of donorspecific antibodies directed at anti-HLA-A, -B, -DR, and -DQ antigens, the particular role of anti-HLA-C donorspecific antibodies in allograft longevity is not yet clear. Recently, preformed anti-native HLA-C donorspecific antibodies were reported to be possibly linked to poor allograft outcome. In addition, inclusion of HLA-C in all transplant allocation regimens has been suggested. Moreover, possible relevance of HLA-C has been shown in other fields (eg, transfusion and obstetrics). Its reduced expression could explain the diminished immunogenicity of the anti-HLA-C antibodies with subsequent lowered strength and prevalence. Furthermore, the"missed self" theory has gained interest. Here, we investigated HLA-C donorspecific antibody immunogenicity, pathogenicity, cellsurface expression, antibody heterogenicity, and possible management tools.