Alloimmune Response Against Donor Glutathione S-Transferase T1 Antigen in Renal Transplant Recipients

Abstract

The long-term outcome of kidney transplantation could be influenced by the appearance of antibodies against donor-specific antigens. Glutathione S-transferase T1 (GSTT1) is a protein preferentially expressed in liver and kidney cells. Deletion of the GSTT1 gene results in a complete lack of protein expression, which occurs in 20% of the white population. GSTT1 donor-recipient mismatch has been deleterious in liver transplantation. The purpose of this study is to examine immunologic and clinical consequences of a GSTT1 donor-recipient mismatch in kidney transplantation. The presence of anti-GSTT1 antibodies was studied retrospectively in sera from 135 patients who underwent transplantation before 1995. Samples from 89 patients who received a GSTT1-positive kidney graft between December 1998 and May 2001 were collected prospectively. GSTT1 genotypes and anti-GSTT1 antibodies were studied by using standard methods. Seven patients, all with the null genotype, produced anti-GSTT1 antibodies. No transplant recipient with a positive genotype produced these antibodies. Six of 7 patients with antibodies also were positive for hepatitis C virus. Clinical outcomes of these patients did not differ from those of the entire group. After kidney transplantation, some patients with the null GSTT1 genotype who received a GSTT1-positive graft developed an immune response, with production of anti-GSTT1 antibodies. The presence of these antibodies did not seem to produce functional impairment in the graft. Hepatitis C virus seems to have a prominent role in this particular allograft immune response.