HA-1 mismatch has significant effect in chronic allograft nephropathy in clinical renal transplantation

The minor histocompatibility antigen HA-1 occurs in two allelic forms: H and R. The HA-1(H) form presented in the context of HLA A2 can elicit specific cytotoxic lymphocyte (CTL) responses and can cause graft-versus-host disease in marrow transplants. However, its significance in solid organ transplants is unknown. We determined whether incompatibility of the HA-1 resulted in enhanced rejection and whether HA-1 specific CTLs were generated.

HLA A2-matched donor/recipient pairs were selected and typed for HA-1 antigens by polymerase chain reaction. Nineteen of 81 pairs were mismatched for HA-1. Peripheral blood mononuclear leucocytes from five recipients, HLA A2 DR-matched with donors, were stimulated for 3 days with third-party donor, matched for HLA A2 DR but mismatched for HA-1. Cells were stained for surface markers, HA-1(H)-specific tetramer reagent, and analyzed by flow cytometry. Controls were unstimulated cells; PBML from two patients never exposed to HA-1(H); immunoglobulin G isotype-matched controls. For all patients, acute rejection rates posttransplant was ascertained. Long-term data was available for 36 patients.

There was no difference in acute rejection rates between the HA-1-matched and -mismatched groups, but there was a significant difference in chronic rejection rates, evidenced by increased graft failures during the follow-up period (P = .0024). Lymphocytes from five HA-1-mismatched recipients were stimulated in vitro with cells from HLA-A2 and DR-matched but HA-1-mismatched surrogate donor. Though there seemed to be an excess of tetramer-positive cells, anti-HA-1-specific CTL responses were not conclusively elicited in vitro.