A study of cytokine gene polymorphisms and protein secretion in renal transplantation

Although there is evidence that cytokine gene polymorphisms are associated with varying quantities of cytokine protein production, the exact role of t hese polymorphisms in allograft rejection remains unclear. In a previous st udy, we demonstrated a significant association between high IL-10 secretion in mixed lymphocyte culture (MLC), together with HLA mismatching for at le ast 4-6 antigens, with the occurrence of acute rejection following renal tr ansplantation. We, therefore, wished to ascertain whether cytokine gene pol ymorphisms are associated with varying levels of protein secretion and/or a llograft rejection in the same group of patients. Cytokine protein secretio n in MLC fur IG-4, IL-6, IL-10 and IFN-gamma was measured by ELISA in 49 pa tient-donor pairs. Protein secretion for the above cytokines was also measu red in phytohaemagglutinin (PHA) stimulated cultures in 30 normal controls. In both patient and control groups, single nucleotide polymorphism analysi s for IL-4 G(- 590)T, IL-6 G(- 174)C, IL-10 G(- 1082)A, IL-10 C(- 819)T, IL -10 C(- 592)A, TNF-alpha G(- 308)A and microsatellite analysis for IFNG (CA repeat) was performed. No correlation was found between cytokine gene poly morphisms and cytokine protein secretion in either mitogen stimulated cultu res (control group) or MLC (patient group). In addition, no correlation was demonstrated between cytokine gene polymorphisms and renal allograft rejec tion. (C) 2001 Elsevier Science B.V. All rights reserved.