Relationship between soluble CD25 and gene expression in healthy individuals and patients with multiple sclerosis

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Abstract

Genome wide association studies and fine mapping has established a firm link between the IL2RA gene, encoding the interleukin-2 receptor α-chain CD25, and susceptibility to multiple sclerosis (MS).

We hypothesized that gene expression in peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and MS patients are associated with IL2RA SNP rs2104286 and that gene expression levels correlate with soluble CD25 (sCD25) concentrations – that are affected by rs2104286.

We used the Affymetrix Human Gene ST 1.0 microarray to analyze gene expression levels in PBMCs from 18 HCs and 51 MS patients. Plasma concentrations of sCD25 were measured by ELISA in all individuals.

In HCs 266 genes correlated with sCD25 with Spearman's rho ≥ 0.707; 70 of these genes had a false discovery rate (FDR) value of q < 0.05. These genes were highest expressed in cells belonging to the innate immune system. Gene-networks were focused around NFKB1, TNF, BCL6 and STAT1. Eighteen genes correlated with sCD25 with rho ≥ 0.707 in relapsing remitting MS versus 33 in secondary progressive and 34 in primary progressive MS. None had a FDR < 0.05. Thirty-eight and 23 genes were differentially expressed between rs2104286 genotype-groups in MS patients and HCs respectively, however they were not significant after FDR correction.

Our study indicates that rs2104286 influences gene expression in PBMCs in HCs as shown by the high correlations with the rs2104286-affected sCD25 protein. Correlations were strongest in HCs suggesting that immunological alterations may obscure the role of the IL2RA SNP rs2104286 in established MS.

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