Publication date: Nov 14, 2018
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.
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.
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.
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.
Open Access PDF
Berge, T., Eriksson, A., Brorson, I.S., Hogestol, E.A., Berg-Hansen, P., Doskeland, A., Mjaavatten, O., Bos, S.D., Harbo, H.F., and Berven, F. Quantitative proteomic analyses of CD4 and CD8 T cells reveal differentially expressed proteins in multiple sclerosis patients and healthy controls. 17989. 2018 Clin Proteomics (16):