title: Glutathione S-transferase T1 mismatch constitutes a risk factor for de novo immune hepatitis after liver transplantation.
abstract: A new form of autoimmune hepatitis referred to as de novo, has been reported after liver transplantation during the past 5 years. The features are identical to those of classical autoimmune hepatitis (AIH), but the facts involved in the onset and outcome of this type of graft dysfunction are still unclear. The identification of antibodies directed to glutathione S-transferase T1 (GSTT1) in the sera of patients with de novo immune hepatitis led us to the description of an alloimmune reaction due to a GSTT1 genetic incompatibility between donor and recipient. We analyzed a cohort of 110 liver transplant patients treated in the liver transplant unit of our hospital during a period of 1 year, from September 2002 to October 2003. We found the following distribution of the GSTT1 genotypes (recipient/donor): +/+ = 66, +/- = 23, -/+ = 15, -/- = 6. Six of these patients were diagnosed with de novo immune hepatitis; all of them belong to the group of negative recipients with positive donors, and all produced anti-GSTT1 antibodies. This genetic combination is associated with a statistically significant increased risk of de novo immune hepatitis (IH) in liver transplant patients (P < .0001 by the Fisher exact test). In conclusion, our results clearly establish the importance of the GSTT1 genotype from donor and recipient of a liver transplant as a predictive marker for de novo IH. At the same time, we confirmed our initial results that only this particular donor/recipient combination triggers the anti-GSTT1 antibody production.
authors.affiliation: Servicios de Inmunología, Hospital Universitario Virgen del Rocío, Servicio Andaluz de Salud, Seville, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Aguilera
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sousa
authors.forename: Francisco
authors.initials: F
authors.lastname: Gavilán
authors.forename: Angel
authors.initials: A
authors.lastname: Bernardos
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Wichmann
authors.forename: Antonio
authors.initials: A
authors.lastname: Nuñez-Roldán
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000032:analysis; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005982:Glutathione Transferase / Q000235:genetics* / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase