CCR5 deletion mutation and its association with the risk of developing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Abstract

BACKGROUND AND OBJECTIVES: Recently published data have suggested a potential role of CC chemokine receptor-5 (CCR5) in a mouse model of graft-versus-host disease (GvHD). It has also been described that a 32-nucleotide deletion within the CCR5 gene (CCR5Delta32) leads to complete loss of functional CCR5 in subjects homozygous for this mutation and decreased expression in heterozygous individuals. We analyzed CCR5 genotypes and their relationship to transplant outcome. DESIGN AND METHODS: A total of 349 individuals, comprising 186 recipients and 163 donors of allogeneic hematopoietic stem cell transplants, were typed for CCR5 polymorphisms. RESULTS: Recipients carrying the CCR5Delta32 allele developed acute GvHD (grades I-IV) less frequently than did patients lacking the CCR5 deletion mutation (11/35 vs. 76/151, p=0.033). This association was still valid after correcting for other known variables (recipient age, donor-recipient gender relation, type of donor, conditioning regimen, diagnosis, stem cell source and GvHD prophylaxis) by logistic regression (OD=0.391, p=0.023). Transplantation from a donor other than a matched sibling (OD=2.007, p=0.028), recipient age (OD=2.117, p=0.041) and myeloablative conditioning regimen (OD=2.235, p=0.014) were found to be factors associated with an increased risk of GvHD. Moreover, acute GvHD symptoms were not observed in any of the recipients carrying the CCR5Delta32 allele transplanted from donors with this deletion mutation (0/11 vs. 70/151, p=0.002). INTERPRETATION AND CONCLUSION: The presence of the CCR5Delta32 allele in recipients constituted an independent and protective factor associated with a decreased risk of GvHD. This protective effect of the CCR5 deletion mutation was particularly marked in patients transplanted from donors also carrying the CCR5Delta32 allele.