A UGT2B17-positive donor is a risk factor for higher transplant-related mortality and lower survival after bone marrow transplantation.
We recently identified a human minor histocompatibility (H) antigen, encoded by UDP glycosyltransferase 2 family, polypeptide B17 (UGT2B17), whose immunogenicity results from differential expression in donor and recipient cells as a consequence of a homozygous deletion of the UGT2B17 gene. UGT2B17 is highly expressed in the liver and colon, which are major targets for graft-versus-host disease (GVHD). To assess the significance of homozygous UGT2B17 gene deletion in allogeneic haematopoietic stem cell transplantation (HSCT), we analysed DNA from 435 stem cell transplant recipients with a haematological malignancy and their human leucocyte antigen-identical unrelated bone marrow donors using sequence-specific primer polymerase chain reaction. Homozygous deletion of the UGT2B17 gene was observed in 85% of normal donors and in 82% of patients. The analysis showed no significant association between UGT2B17 mismatch in the GVHD direction and the incidence of acute GVHD, chronic GVHD, relapse, or survival. However, the use of a UGT2B17-positive donor was an independent risk factor for higher transplant-related mortality and lower survival after transplantation. UGT2B17 is a metabolic enzyme for hormones, drugs, and potentially toxic exogenous compounds and is expressed in subsets of haematopoietic cells. Thus, the enzyme function of UGT2B17 in donor cells may affect the outcome of allogeneic HSCT.
Terakura
Seitaro
S
Department of Haematology, Nagoya University Graduate School of Medicine, Aichi, Japan.
Murata
Makoto
M
Nishida
Tetsuya
T
Emi
Nobuhiko
N
Akatsuka
Yoshiki
Y
Riddell
Stanley R
SR
Morishima
Yasuo
Y
Kodera
Yoshihisa
Y
Naoe
Tomoki
T
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003106:Colon; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000401:mortality; D015996:Survival Rate; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D015778:Minor Histocompatibility Antigens; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human