Abstrakt

In multiple myeloma (MM) patients, various T-cell abnormalities, such as a marked reduction in the proportions of CD4 and CD8 cells expressing co-stimulatory molecules, signal transduction components, Th1/Th2 imbalance and alterations of regulatory T cells/T helper 17 cells (Treg/Th17 ratio), have been observed. The inducible T-cell co-stimulator (ICOS) has been implicated in the induction and regulation of Th1, Th2, and Treg/Th17 immunity. Therefore, we postulate that variations in ICOS gene might be associated with susceptibility and clinical course of MM. We analyzed ICOSISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.602A>C (rs10183087), ICOSc.1564T>C (rs4404254) and ICOSc.2373G>C (rs4675379) polymorphisms in 205 MM patients and 325 controls with TaqMan® SNP Genotyping Assays. None of the investigated ICOS gene polymorphisms were associated with susceptibility to the disease. However, in a multivariate Cox analysis which included the age of diagnosis, ISS, time to the clinical response to the treatment, gender, immunoglobulin classes, ICOS gene variations, we found that time to the response to treatment, ISS stage 3 and possessing of ICOSc.2373G>C [C+] allele were independently associated with the overall survival (HR: 1.35, 2.86 and 3.77, respectively). Although the result of the present study does not confirm the association of the investigated polymorphisms with risk of MM, they indicated that variations in ICOS gene might influence overall survival.

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