Natalizumab Therapy Modulates miR-155, miR-26a and Proinflammatory Cytokine Expression in MS Patients.
MicroRNAs fine-tune the regulation of Th1/Th17 lymphocyte subsets in multiple sclerosis. We investigated the expression of miRNAs (previously associated with mycobacterial and viral infections) in MS patients and healthy donors (HD) following 6 months natalizumab therapy. In addition, Th1/Th17 cytokines and the presence of anti-EBNA1/VCA IgG in MS patients with different pattern of miRNA expression have been evaluated. MiR-155, miR-26a, miR-132, miR-146a and Th1/Th17 cytokines expression was detected by RT-real time PCR; moreover anti-EBNA1 and VCA IgG titres were measured by ELISA. We observed an up-regulation of miR-155 (p value = 0.009) and miR-132 (p value = 0.04) in MS patients compared to HD. In MS patients, IL-17a (p = 0.037), IFN γ (p = 0.012) and TNFα (p = 0.015) but not IL-6 were over-expressed compared to HD. Two different miRNAs patterns associated to the expression of different cytokines were observed in the MS cohort. Moreover, a down-regulation of miR-155 and miR-26a was seen in MS patients during and after natalizumab therapy. MS patients that over-expressed miR-155 showed a higher EBNA1 IgG titer than MS patients with high levels of miR-26a. In conclusions the expression of particular miRNAs modulates the pro-inflammatory cytokine expression and the humoral response against EBV and this expression is natalizumab regulated.
Department of Medical Sciences, University of Sassari, Sassari, Italy.
Giuseppe
G
Mameli
Department of Experimental Medicine, University of Sassari, Sassari, Italy.
Giannina
G
Arru
Department of Medical Sciences, University of Sassari, Sassari, Italy.
Elisa
E
Caggiu
Department of Medical Sciences, University of Sassari, Sassari, Italy.
Magdalena
M
Niegowska
Department of Experimental Medicine, University of Sassari, Sassari, Italy.
Stefania
S
Leoni
Department of Experimental Medicine, University of Sassari, Sassari, Italy.
Giordano
G
Madeddu
Department of Experimental Medicine, University of Sassari, Sassari, Italy.
Sergio
S
Babudieri
Department of Experimental Medicine, University of Sassari, Sassari, Italy.
Gian Pietro
GP
Sechi
Department of Medical Sciences, University of Sassari, Sassari, Italy.
Leonardo A
LA
Sechi
D000328:Adult; D016207:Cytokines / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D020381:Interleukin-17 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D000069442:Natalizumab / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D020381:Interleukin-17; D015850:Interleukin-6; D035683:MicroRNAs; D000069442:Natalizumab; D014409:Tumor Necrosis Factor-alpha; C508717:IL17A protein, human; C524942:MIRN155 microRNA, human; C528163:MIRN26 microRNA, human; C417029:EBV-encoded nuclear antigen 1