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

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

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.

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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):

Concepts Keywords
Autoimmune Genotype
Blood Proteomics
Blood Brain Barrier CTLA-4
CD28 Multiple sclerosis
CD4 T helper cell
CD8 Proteomics
Central Nervous System T cell
Correlation Relapsing–remitting
CTLA4 Immunology
Demyelination Immune system
Differential Medicine
Electrospray Medical specialties
Etiology Branches of biology
Genetic Inflammation
Genotype MS
HLA Disease
Immune Cell System demyelination
Inflammation Multiple sclerosis
Liquid Chromatography
Loci
Multiple Sclerosis
Nerve
Pathogenesis
Polymorphisms
Proteomic
Proteomics
Proximal
T Cell
Tandem Mass Spectrometry

Semantics

Type Source Name
disease MESH Autoimmunity
gene UNIPROT CD28
gene UNIPROT CTLA4
disease DOID relapsing-remitting MS
gene UNIPROT FBN1
disease MESH demyelination
disease MESH inflammation
disease DOID multiple sclerosis
disease MESH multiple sclerosis
gene UNIPROT CD8A
gene UNIPROT CD4

Original Article

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