Low DPP4 expression and activity in multiple sclerosis

Clin Immunol. 2014 Feb;150(2):170-83. doi: 10.1016/j.clim.2013.11.011. Epub 2013 Nov 28.

Abstract

Multiple sclerosis (MS) is a prototypic Th1/Th17 chronic autoimmune disease of the central nervous system. Dipeptidyl peptidase 4 (DPP4 or CD26) is a multifunctional molecule involved in autoimmune diseases' pathophysiology. We sought to integrate disparate pieces of data and analyze the plasma levels of sDPP4, DPP activity and DPP4 surface expression on T-cells in 129 MS patients with different clinical forms and 53 healthy controls, across two independent cohorts. Herein, we provide new evidence that sDPP4 concentration and DPP activity are significantly lower in MS patients than controls (p < 0.0001 and p < 0.01, respectively). In contrast, the frequency of circulating CD8(+)DPP4(hi) T-cells (p = 0.02) was increased in MS patients. This is the first study that simultaneously analyzes DPP4 expression and function in a large cohort of MS patients. Our data indicate a putative role for DPP4 in MS pathophysiology and suggest that a deeper understanding of surface versus shed DPP4 biology is warranted.

Keywords: Biomarker; CD26; Clinical activity; Dipeptidyl peptidase 4; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Dipeptidyl Peptidase 4 / genetics*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Female
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism*
  • Phenotype
  • ROC Curve
  • Receptors, Antigen, T-Cell / metabolism
  • Reproducibility of Results
  • Sex Factors
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Vitamin D / blood

Substances

  • Biomarkers
  • Receptors, Antigen, T-Cell
  • Vitamin D
  • Dipeptidyl Peptidase 4