No differential gene expression for CD4+ T cells of MS patients and healthy controls

Abstract

Background: Multiple sclerosis-associated genetic variants indicate that the adaptive immune system plays an important role in the risk of developing multiple sclerosis. It is currently not well understood how these multiple sclerosis-associated genetic variants contribute to multiple sclerosis risk. CD4⁺ T cells are suggested to be involved in multiple sclerosis disease processes.

Objective: We aim to identify CD4⁺ T cell differential gene expression between multiple sclerosis patients and healthy controls in order to understand better the role of these cells in multiple sclerosis.

Methods: We applied RNA sequencing on CD4⁺ T cells from multiple sclerosis patients and healthy controls.

Results: We did not identify significantly differentially expressed genes in CD4⁺ T cells from multiple sclerosis patients. Furthermore, pathway analyses did not identify enrichment for specific pathways in multiple sclerosis. When we investigated genes near multiple sclerosis-associated genetic variants, we did not observe significant enrichment of differentially expressed genes.

Conclusion: We conclude that CD4⁺ T cells from multiple sclerosis patients do not show significant differential gene expression. Therefore, gene expression studies of all circulating CD4⁺ T cells may not result in viable biomarkers. Gene expression studies of more specific subsets of CD4⁺ T cells remain justified to understand better which CD4⁺ T cell subsets contribute to multiple sclerosis pathology.

Keywords: CD4+ T cells; Genetics; RNA sequencing; gene expression; multiple sclerosis.

Figure 1.

Boxplots of the five most consistently differentially expressed genes in CD4⁺ T cells from multiple sclerosis (MS) patients compared to healthy controls (HC). (a) RPL21P16; (b) RBM27; (c) CAMK4; (d) LIMK2; (e) CLUAP1. Individual expression levels are presented for healthy controls (square dots) and MS patients (triangular dots). The boxes delimit 25% and 75% of the values; the horizontal bars represent the median value. The whiskers represent values that do not exceed a distance of 1.5 times the interquartile range from the middle 50% of the data.