TY - JOUR
T1 - Glutathione S-transferase T1-null seems to be associated with graft failure in hematopoietic SCT
AU - Elhasid, R.
AU - Krivoy, N.
AU - Rowe, J. M.
AU - Sprecher, E.
AU - Efrati, E.
N1 - Funding Information:
The authors thank Mrs Osnat Gidoni, MSc, for her technical help. This study was funded in part by a grant from the Israel Cancer Association in the name of Israel Jacob and Lila Halter (number 20090070).
PY - 2010/12
Y1 - 2010/12
N2 - Hematopoietic SCT (HSCT) from HLA-matched donors is sometimes complicated by GVHD or graft rejection, because of mismatched mHA. This study presents data suggesting the involvement of glutathione S-transferase theta-1 (GSTT1), a phase II detoxifying enzyme encoded by GSTT1, in Ab-mediated rejection of HSCT in children with congenital hemoglobinopathies (CHs). Mismatch of GSTT1, which often features a deletion polymorphism variant, can have major consequences in solid organ transplantation outcome. In liver transplantation, it has been shown to lead to de novo hepatitis, whereas in kidney transplantation, chronic allograft rejection has been documented. In this study on 18 children with CH who underwent HSCT, five cases of graft rejection occurred, all in GSTT1-null patients, four of which featured anti-GSTT1 antibodies. The data suggest that when GSTT1-null patients are transplanted with a GSTT1-positive graft, rejection due to an Ab-mediated immune response against GSTT1 displayed on transplanted stem cells may take place. Thus, it seems that detection of anti-GSTT1 antibodies in patients with a GSTT1-null genotype before transplantation may be predictive of graft rejection in the event of a GSTT1-positive donor.
AB - Hematopoietic SCT (HSCT) from HLA-matched donors is sometimes complicated by GVHD or graft rejection, because of mismatched mHA. This study presents data suggesting the involvement of glutathione S-transferase theta-1 (GSTT1), a phase II detoxifying enzyme encoded by GSTT1, in Ab-mediated rejection of HSCT in children with congenital hemoglobinopathies (CHs). Mismatch of GSTT1, which often features a deletion polymorphism variant, can have major consequences in solid organ transplantation outcome. In liver transplantation, it has been shown to lead to de novo hepatitis, whereas in kidney transplantation, chronic allograft rejection has been documented. In this study on 18 children with CH who underwent HSCT, five cases of graft rejection occurred, all in GSTT1-null patients, four of which featured anti-GSTT1 antibodies. The data suggest that when GSTT1-null patients are transplanted with a GSTT1-positive graft, rejection due to an Ab-mediated immune response against GSTT1 displayed on transplanted stem cells may take place. Thus, it seems that detection of anti-GSTT1 antibodies in patients with a GSTT1-null genotype before transplantation may be predictive of graft rejection in the event of a GSTT1-positive donor.
KW - GSTT1 genotype
KW - HSCT
KW - anti-GSTT1 antibodies
KW - congenital hemoglobinopathy
KW - rejection
UR - http://www.scopus.com/inward/record.url?scp=78650190919&partnerID=8YFLogxK
U2 - 10.1038/bmt.2010.61
DO - 10.1038/bmt.2010.61
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C2 - 20348973
AN - SCOPUS:78650190919
SN - 0268-3369
VL - 45
SP - 1728
EP - 1731
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 12
ER -