OR45: INTERLEUKIN-1 RECEPTOR (IL1-R): ROLE IN ANTI-CYTOMEGALOVIRUS (CMV) IMMUNE RESPONSE AND PROTECTION AGAINST CMV REACTIVATION AFTER ALLOGENEIC HEMATOPOETIC CELL TRANSPLANTATION

Abstract

Aim An immunocompromised state after hematopoietic cell transplantation (HCT) leads to a deficient anti-cytomegalovirus (CMV) immune response. This often culminates into episodes of posttransplant CMV reactivation and complications. Cytokines and their receptors act as chief mediators of anti-viral immune response. Genetic control of cytokine production is evidenced by polymorphisms in cytokine gene regulatory regions resulting in low, moderate, or high cytokine production profiles. In the present investigation, we assessed whether gene variants of cytokine or their receptors influences post HCT CMV complications and anti-CMV immune response. Methods A total of 240 allogeneic HCT donors and 50 healthy individuals were genotyped for 22 single nucleotide variants located in the regulatory and/or exonic regions of 13 cytokine or cytokine receptor genes. CMV specific immune response was assessed by stimulating PBMNCs from healthy individuals with CMV lysate and CMV peptide-pp65 followed by enumeration of IFN-γ producing and CD107a expressing (degranulating) MNCs, T cells and their subsets. Results Allogeneic HCT recipients receiving grafts from donors carrying low IL-1R producing genotype (-1970 CC) had high incidence of CMV reactivation (p = 0.01; Hazard ratio = 2.1, Fig. 1 ) in comparison to the HCT recipients receiving grafts from donors carrying high IL1-R producing genotype (-1970 TT). Further, the analysis in healthy individuals showed that IL1R+ cells have 3-5-fold stronger anti-CMV immune response (IFNγ+ and/or CD107a+ cells) in comparison to IL1R- cells. Conclusions High IL-1R producing gene variants confer strong protection against CMV reactivation after allogeneic HCT. The conclusions are further supported by the finding that anti-CMV immune response is dominated by IL1R+ MNCs.