Clinical relevance of GSTT1 mismatch in solid organ and hematopoietic stem cell transplantation

• Published in: Human immunology Vol. 74; no. 11; pp. 1470 - 1473
• Main Authors: Aguilera, Isabel, Sousa, Jose Manuel, Núñez-Roldán, Antonio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Allergy and Immunology; Antibodies - blood; Genetic Predisposition to Disease; Glutathione Transferase - genetics; Glutathione Transferase - immunology; Graft Rejection - etiology; Graft Rejection - immunology; Graft vs Host Disease - etiology; Graft vs Host Disease - immunology; Hematopoietic Stem Cell Transplantation; Hepatitis - etiology; Hepatitis - immunology; Humans; Isoantigens - genetics; Isoantigens - immunology; Liver Transplantation; Polymorphism, Genetic; Postoperative Complications - immunology; Ab; GSTM1; mHag; antibody; minor histocompatibility antigen; Glutathione S-transferase theta 1; LT; hematopoietic stem cell transplantation; GSTT1; Glutathione S-transferase mu 1; liver transplant; HSCT
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2013.06.004

Abstract Since 2001, year in which Glutathione S-transferase theta class 1 (GSTT1) gene appeared to be related to the occurrence of de novo immune hepatitis after liver transplantation, this gene with two allelic variants, GSTT1∗ A (wild type copy) and GSTT1∗ 0 (deletion copy), has emerged as a potent histocompatibility antigen. Namely, a donor-recipient liver graft combination of a GSTT1-negative recipient (homozygous for GSTT1∗ 0 ) and a GSTT1-positive donor results, very frequently, in the appearance of a severe immune-related graft hepatitis with production of IgG anti-GSTT1 antibodies. In kidney transplantation, GSTT1 donor-recipient mismatch is also associated with production of anti-GSTT1 antibodies and antibody-related rejection episodes with C4d deposition in graft biopsy. The more recent discovery of anti-GSTT1 antibodies in hematopoietic stem cell transplantation, clearly confirms a role of GSTT1 as histocompatibility antigen in this setting. Interestingly, the consequences of GSTT1 mismatch might be either rejection or graft-versus-host disease, depending on the GSTT1 mismatch’s sense of direction. The involvement of GSTT1 in immunological allo-recognition is unquestionable although there are still many aspects that remain to be explored.