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TITLE: GLUTATHIONE S-TRANSFERASE T1 (GSTT1) POLYMORPHISM IS A HISTOCOMPATIBILITY SYSTEM IN LIVER AND KIDNEY TRANSPLANTATION

Isabel Aguilera, M. Francisca Gonzalez-Escribano, J. Manuel Sousa, Angel Bernardos, Miguel A. Gentil, Ingeborg Wichmann and Antonio Nunez-Roldan.

¹Servicio de Inmunologia, Hospital Universitario Virgen del Rocio, Sevilla, Spain.

Glutathione S-transferase T1 (GSTT1) is part of a group of isoenzymes involved in the cellular detoxification of both xenobiotic and endobiotic compounds which is preferentially expressed on liver and kidney cells. Deletions of GSTT1 gene (null/null genotype) resulting in a complete lack of protein expression occur in 11 to 58% of individuals from different ethnic origin. We have recently demonstrated that liver transplant recipients who are negative (null/null) for GSTT1 and receive a liver graft from a GSTT1+ donor, could produce antibodies against GSTT1 and develop a "de novo" hepatitis leading to a severe liver dysfunction. To further investigate the role of GSTT1 polymorphism in clinical transplantation, eight patients from a total of 300 liver-transplant recipients from our center who developed a "de novo" immune-mediated hepatitis approximately 2 years after transplantation were included in this study. When the GSTT1 genotype of the 8 donor-recipient pairs were analysed, we found that this gene was absent from all recipients and present in all the liver donors. In all the cases, antibodies against recombinant GSTT1 protein were present in patient sera. Preliminary studies on the role of this genetic system on kidney transplant demonstrated the presence of anti-GSTT1 antibodies in 4 out of 8 GSTT1-negative renal patients with a functional kidney graft. Such antibodies were absent before transplantation. Although the clinical consequences of this fact are now under evaluation and a prospective study is being conducted, we suggest that GSTT1 protein represents a histocompatibility barrier in liver as well as in kidney transplantation.