학술논문

Association of cytokine single nucleotide polymorphisms with B7 costimulatory molecules in kidney allograft recipients.
Document Type
Article
Source
Pediatric Transplantation. Feb2002, Vol. 6 Issue 1, p69-77. 9p.
Subject
*GENETIC polymorphisms
*KIDNEY transplantation
*HOMOGRAFTS
Language
ISSN
1397-3142
Abstract
Abstract: 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-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6, IL-10, and transforming growth factor-β (TGF-β). 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. Abstract: African–American race is associated with an increased risk of allograft loss,... [ABSTRACT FROM AUTHOR]