title: Low DPP4 expression and activity in multiple sclerosis.
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.
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain. Electronic address: marta.tejera.alhambral@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Tejera-Alhambra
authors.affiliation: Centre d'Immunologie Humaine, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France; INSERM U818, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France. Electronic address: armanda.casrouge@pasteur.fr.
authors.forename: Armanda
authors.initials: A
authors.lastname: Casrouge
authors.affiliation: Department of Neurology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain. Electronic address: claradeandres@hotmail.com.
authors.forename: Clara
authors.initials: C
authors.lastname: de Andrés
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain. Electronic address: rrm-83@hotmail.com.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ramos-Medina
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain. Electronic address: barbara.alonso@hotmail.com.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Alonso
authors.affiliation: Center Alicia Koplowitz for Multiple Sclerosis of the Community of Madrid, Bulevar de José Prat, 42, 28032 Madrid, Spain. Electronic address: janet.vega@hotmail.com.
authors.forename: Janet
authors.initials: J
authors.lastname: Vega
authors.affiliation: Centre d'Immunologie Humaine, Department of Immunology, Institut Pasteur, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France; INSERM U818, 25 Rue du Docteur Roux, 75724 Paris Cedex 15, France. Electronic address: albertm@pasteur.fr.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain. Electronic address: ssramon@salud.madrid.org.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sánchez-Ramón
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D012372:ROC Curve; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015203:Reproducibility of Results; D012737:Sex Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014807:Vitamin D / Q000097:blood
chemical_list: D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell; D014807:Vitamin D; D018819:Dipeptidyl Peptidase 4
keywords: Biomarker; CD26; Clinical activity; Dipeptidyl peptidase 4; Multiple sclerosis