Association of cytokine single nucleotide polymorphisms with B7 costimulatory molecules in kidney allograft recipients.
African-American race is associated with an increased risk of allograft loss, suggesting that African-American patients may form an immunologically higher risk group. Previously, we demonstrated that immune cell costimulatory molecule expression is significantly higher in African-Americans than in Caucasians. Polymorphic variations in the genes for cytokines have been associated with a number of immunological conditions, and with transplant rejection. This study was performed to determine the distribution, in African-American and Caucasian renal transplant recipients, of single nucleotide polymorphisms (SNPs) in the following cytokine genes: tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin (IL)-6, IL-10, and transforming growth factor-beta (TGF-beta). Cytokine production from blood cells was determined, and cell-surface B7 (CD80, CD86) expression was measured. There was a significant link between IL-10 genotype and acute rejection episodes, but only in African-American patients (p < 0.01). Also, African-American patients had a significantly higher probability of having the IL-6 G-allele (p < 0.0001), which is associated with a high production of IL-6 protein. Incubation of blood cells with IL-6 resulted in increased expression of surface CD80 and CD86, while IL-10 decreased CD80 expression. This study demonstrated a clear correlation of the IL-6 G-allele with increased cellular CD80 expression and the IL-10 G-allele with decreased CD80 expression. These data raise the possibility that specific genotypes are associated with local cytokine regulation of cell-surface costimulatory molecule expression. African-American patients may have a genetically determined, quantitatively different immune response than Caucasian patients, contributing to adverse transplant outcomes.
Hutchings
A
A
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA. ahutchings@peds.uab.edu
Guay-Woodford
L
L
Thomas
J M
JM
Young
C J
CJ
Purcell
W M
WM
Pravica
V
V
Perrey
C
C
Hutchinson
I V
IV
Benfield
M R
MR
D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D009711:Nucleotides / Q000235:genetics*; D011110:Polymorphism, Genetic; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D014184:Transplantation, Homologous; D001741:Black or African American
D016207:Cytokines; D009711:Nucleotides