Increased severity of acute graft versus host disease as a result of differential expression following a homozygous gene deletion.
Acute graft versus host disease (aGvHD) is a major cause of early morbidity post-haematopoietic stem cell transplantation with minor histocompatibility antigens being a contributing factor. One mHA encoded by the UDP glycosyltransferase 2 family polypeptide B17 (UGT2B17) gene has been shown to be immunogenic because of differential expression in the donor and recipient. We investigated the effects of a homozygous gene deletion of UGT2B17 on the severity of acute aGvHD post-HSCT in HLA-matched related donors. 115 donor and recipient HLA and UGT2B17 genotypes were determined using PCR-SSO and PCR-SSP, respectively. aGvHD grading was determined using routine criteria and dichotomized into either nonclinically significant (0-I) or clinically significant (II-IV). For all analyses, P-values of ≤ 0.05 were considered significant. The frequency of the gene deletion within the total cohort tested was 29.1%. A significant increase in aGvHD severity (grades II-IV) was seen in UGT2B17 recipients expressing the protein when transplanted with a UGT2B17 disparate donor (P = 0.011). We observed a significant association between UGT2B17 expressing recipients and UGT2B17 deficient donors with the severity of aGvHD. This study provides additional evidence that genomic variations may predispose to more severe aGvHD, but are not a mechanism for GvHD.
Transplantation Laboratory, Manchester Royal Infirmary, Manchester, UK. steven.jervis@cmft.nhs.uk
S
S
Jervis
P
P
Collins
D
D
Tate
L
L
Foster
V
V
Bowman
C
C
Adhern
A
A
Bloor
J
J
Yin
R
R
Wynn
K
K
Poulton
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000276:immunology*; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D009842:Oligopeptides / Q000235:genetics; D055815:Young Adult
C110615:HA-1 antigen; C524866:HLA-A*02 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human