Molecular mismatch load distribution in the United States is driven more by recipient genotype than regional donor pool composition

Molecular HLA matching has been shown to more precisely predict organ transplantation outcome than antigen matching, which is still in use by major organ allocation programs. Although optimizing allocation for molecular matching promises increased utility of the scarce resource, it may introduce imbalances in access to transplantation, and may thus not be feasible for all patients given their corresponding local donor pool. To understand the impact of donor pool composition in different geographic regions of the United States, a simulation of PIRCHE-T2 and PIRCHE-B molecular mismatch load (MML) distributions has been performed. Although our data indicates regional variation of estimated molecular mismatch load, the effect appears to be more dependent on the patient HLA genotypes rather than the donor pool. Patient-specific differences in empirical cumulative MML distributions indicate a need for adjustment of histocompatibility-based allocation to prevent disadvantages of minorities. Simulations reflective of the entire allocation process are required to confirm allocation equity can be achieved whilst optimizing for MML.