Quantitative proteomic analyses of CD4(+) and CD8(+) T cells reveal differentially expressed proteins in multiple sclerosis patients and healthy controls

BACKGROUND: Multiple sclerosis (MS) is an autoimmune, neuroinflammatory disease, with an unclear etiology. However, T cells play a central role in the pathogenesis by crossing the blood–brain-barrier, leading to inflammation of the central nervous system and demyelination of the protective sheath surrounding the nerve fibers. MS has a complex inheritance pattern, and several studies indicate that gene interactions with environmental factors contribute to disease onset. METHODS: In the current study, we evaluated T cell dysregulation at the protein level using electrospray liquid chromatography–tandem mass spectrometry to get novel insights into immune-cell processes in MS. We have analyzed the proteomic profiles of CD4(+) and CD8(+) T cells purified from whole blood from 13 newly diagnosed, treatment-naive female patients with relapsing–remitting MS and 14 age- and sex-matched healthy controls. RESULTS: An overall higher protein abundance was observed in both CD4(+) and CD8(+) T cells from MS patients when compared to healthy controls. The differentially expressed proteins were enriched for T-cell specific activation pathways, especially CTLA4 and CD28 signaling in CD4(+) T cells. When selectively analyzing proteins expressed from the genes most proximal to > 200 non-HLA MS susceptibility polymorphisms, we observed differential expression of eight proteins in T cells between MS patients and healthy controls, and there was a correlation between the genotype at three MS genetic risk loci and protein expressed from proximal genes. CONCLUSION: Our study provides evidence for proteomic differences in T cells from relapsing–remitting MS patients compared to healthy controls and also identifies dysregulation of proteins encoded from MS susceptibility genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12014-019-9241-5) contains supplementary material, which is available to authorized users.