Molecular genetic analysis of interleukin-1 promoter and receptor antagonist tandem repeat polymorphisms among HLA-identical renal transplant recipient and donor pairs.

The cytokine gene polymorphisms as well as the minor histocompatibility antigen (mHAg) disparities have been thought to result in transplant graft rejection and graft-versus-host reaction between HLA-identical donor/recipient pairs. We detected interleukin (IL)-1 promoter and receptor antagonist tandem repeat polymorphisms among 21 HLA identical renal transplant recipient and donor pairs; of 21 pairs, 15 (71%) showed at least one locus difference between donor and recipient, and 73% of the pairs with the disparities at these loci showed either recipient to donor (R-->D) or donor to recipient (D-->R) positive CD4+ cell response measured by a modified Cylex assay developed in our laboratory. Allele 2 of IL-1 receptor antagonist genotype (IL-1ra VNTR), a gene associated with an increasing IL-1beta production, was detected in the three recipients who developed rejections. One HLA-identical pair that had variations on all four loci of IL-1 gene cluster consistently showed positive CD4+ cell immune responses between the donor and the recipient. This study may provide information of the role of non-HLA genes participating in allograft rejection; this demonstrates that in addition to the disparities of the mHAgs, the non-HLA antigens have to be considered as risk factors in HLA-identical solid organ transplantation.