Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations

Abstract

Minor histocompatibility (H) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen-matched solid organ and stem cell transplantation (SCT). Minor H antigens are instrumental in the processes of transplant rejection, graft-versus-host disease, and in the curative graft-versus-tumor effect of SCT. The latter characteristic enabled the current application of selected minor H antigens in clinical immunotherapeutic SCT protocols. No information exists on the global phenotypic distribution of the currently identified minor H antigens. Therefore, an estimation of their overall impact in human leukocyte antigen-matched solid organ and SCT in the major ethnic populations is still lacking. For the first time, a worldwide phenotype frequency analysis of ten autosomal minor H antigens was executed by 31 laboratories and comprised 2,685 randomly selected individuals from six major ethnic populations. Significant differences in minor H antigen frequencies were observed between the ethnic populations, some of which appeared to be geographically correlated.

Figure 1. Geospatial Analyses of the Phenotype Frequencies of HA-1 (A), HA-8 (B), ACC-2 (C), and UGT2B17 (D) in the European White Populations

Red dots represent the centers from which the frequency data were obtained. Numbers in the scaling indicate the proportion of individuals with an immunogenic phenotype.

Figure 2. Estimated Minor H Antigen Disparity Rates

Comparison for sib (A) and MUD (B) transplantations among six different ethnic populations. Data are depicted as the mean disparity rate of the ten analyzed minor H antigens and the standard error. (C) Variation in frequencies of the immunogenic minor H antigen phenotype per minor H antigen.