Dopaminergic receptors and adrenoceptors in circulating lymphocytes as putative biomarkers for the early onset and progression of multiple sclerosis.
Clinically isolated syndrome (CIS) is a first, usually recovering, episode of neurological disturbance(s) suggestive of multiple sclerosis (MS). CIS subjects might benefit from early disease-modifying drugs, provided that those at high risk of developing MS can be identified. Gene expression for dopaminergic receptors (DR) and adrenoceptors (AR) is dysregulated in lymphocytes of MS patients and is affected by treatment with interferon (IFN)-β. In particular, lymphocyte DR D5 mRNA might be a marker of IFN-β response in MS patients. No information exists so far in CIS subjects. We investigated DR and AR gene expression in peripheral blood mononuclear cells (PBMC) and in CD4+ T effector (Teff) and regulatory (Treg) cells from CIS subjects, and assessed their relationship with MS progression after 12months. Expression of several DR and AR are upregulated in PBMC, Teff and Treg from CIS subjects. DR D3 and α2A-AR mRNA in PBMC, and DR D5 mRNA in Treg correlate with the risk of MS at 12months. Results show the involvement of dopaminergic and adrenergic pathways in CIS as well as in MS pathogenesis, supporting the evaluation of dopaminergic and adrenergic agents in MS.
Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy. Electronic address: marco.cosentino@uninsubria.it.
Marco
M
Cosentino
Multiple Sclerosis Center, Hospital 'S. Antonio Abate', Gallarate, VA, Italy.
Mauro
M
Zaffaroni
Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
Massimiliano
M
Legnaro
Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
Raffaella
R
Bombelli
Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
Laura
L
Schembri
Multiple Sclerosis Center, Hospital 'S. Antonio Abate', Gallarate, VA, Italy.
Damiano
D
Baroncini
Multiple Sclerosis Center, Hospital 'S. Antonio Abate', Gallarate, VA, Italy.
Anna
A
Bianchi
Neurological Department, Valduce Hospital, Como, Italy.
Raffaella
R
Clerici
Neurological Department, Valduce Hospital, Como, Italy.
Mario
M
Guidotti
Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
Paola
P
Banfi
Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.
Giorgio
G
Bono
Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
Franca
F
Marino
D000328:Adult; D002395:Catecholamines / Q000652:urine; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology* / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult
D002395:Catecholamines; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D014446:Tyrosine 3-Monooxygenase
Adrenoceptors; CD4+ T effector lymphocytes; CD4+ T regulatory lymphocytes; Clinically isolated syndrome; Dopaminergic receptors; Multiple sclerosis; Peripheral blood mononuclear cells