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Related Concept Videos

Multiple Sclerosis l: Introduction01:19

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Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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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.

Clinical Immunology (Orlando, Fla.)
|January 14, 2014
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Summary

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.

Keywords:
BiomarkerCD26Clinical activityDipeptidyl peptidase 4Multiple sclerosis

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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.