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Updated: May 4, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Low DPP4 expression and activity in multiple sclerosis
Marta Tejera-Alhambra1, Armanda Casrouge2, Clara de Andrés3
1Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain.
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.
Insights
Levels of shed Dipeptidyl peptidase 4 (sDPP4) and its activity are lower in multiple sclerosis (MS) patients. However, T-cells expressing high DPP4 levels increase in MS, suggesting a complex role for DPP4 in this autoimmune disease.
Area of Science:
- Immunology
- Neuroscience
- Biochemistry
Background:
- Multiple sclerosis (MS) is a chronic central nervous system autoimmune disease.
- Dipeptidyl peptidase 4 (DPP4), also known as CD26, is implicated in autoimmune disease pathogenesis.
- Understanding DPP4's role in MS requires analyzing its different forms and functions.
Purpose of the Study:
- To investigate plasma levels of soluble DPP4 (sDPP4), DPP activity, and DPP4 surface expression on T-cells in MS patients.
- To compare these parameters between MS patients and healthy controls across two independent cohorts.
- To elucidate the potential role of DPP4 in the pathophysiology of multiple sclerosis.
Main Methods:
- Analysis of plasma sDPP4 concentration and DPP enzymatic activity in 129 MS patients and 53 healthy controls.
- Flow cytometry assessment of DPP4 surface expression on T-cells, specifically CD8(+) T-cells.
- Comparison of data between MS patient subgroups and controls, validated across two independent cohorts.
Main Results:
- Significantly lower plasma sDPP4 concentrations and DPP activity were observed in MS patients compared to controls (p < 0.0001 and p < 0.01, respectively).
- A significantly higher frequency of circulating CD8(+) T-cells with high DPP4 expression (DPP4(hi)) was found in MS patients (p = 0.02).
- This is the first study to simultaneously analyze DPP4 expression and function in a large MS cohort.
Conclusions:
- The study reveals distinct alterations in shed DPP4 and cell-surface DPP4 in multiple sclerosis.
- Findings suggest a complex, potentially dual role for DPP4 in MS pathophysiology.
- Further research into the differential biology of surface versus shed DPP4 is warranted for a comprehensive understanding of MS.
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01:19Multiple Sclerosis l: Introduction
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