Donor CCR5 Delta32 polymorphism and outcome following cardiac transplantation.
BACKGROUND
Chemokines regulate the recruitment and trafficking of leukocytes during an immune response. Animal models have shown correlations between chemokine production and leukocyte infiltration during allograft rejection. Also, antagonism of chemokine receptors in transplant models has produced prolonged graft survival. Individuals homozygous for a 32 base pair deletion in the CC chemokine receptor 5 (CCR5) gene have an inactive receptor. Renal transplant recipients homozygous for the deletion have been shown to survive significantly longer than those heterozygous or homozygous for the wild type allele. CCR5 ligands are upregulated during allograft rejection aiding infiltration of leukocytes. We investigated the influence of CCR5Delta32 polymorphism on outcome following human cardiac transplantation.


METHODS
Recipients and corresponding donors were genotyped for CCR5Delta32 polymorphism using polymerase chain reactions.


RESULTS
We found no correlation between recipient genotype and outcome following transplantation. However, there was a significant correlation between donor genotype and mortality in patients transplanted for a nonischemic condition (DD = n/a, ID = 4%, II = 25%, P = .0014).


CONCLUSIONS
The induction of CCR5 expression in endomyocardial biopsy tissue is known to correlate with leukocyte graft infiltration. We suggest that donor CCR5 may be more important for leukocyte trafficking during rejection than recipient CCR5 expression. The CCR5 gene is highly conserved, and due to the small population available for this study, more work is required from other centers.
Fildes
J E
JE
Transplant Centre, South Manchester University Hospitals NHS Trust, Manchester M23 9LT, U.K.
Walker
A H
AH
Howlett
R
R
Bittar
M N
MN
Hutchinson
I V
IV
Leonard
C T
CT
Yonan
N
N
D001483:Base Sequence; D017931:DNA Primers; D005838:Genotype; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D012189:Retrospective Studies; D017384:Sequence Deletion; D016019:Survival Analysis; D016896:Treatment Outcome
D017931:DNA Primers; D019713:Receptors, CCR5