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

Abstract

Background: Multiple sclerosis (MS) is an autoimmune, neuroinflammatory disease, with an unclear etiology. How‑ ever, 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 chro‑ matography–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 path‑ ways, 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.