- 4 October 2012
- journal article
- research article
- Published by SAGE Publications in Multiple Sclerosis Journal
- Vol. 19 (7) , 871-876
Abstract
Recently, a polymorphism in the LIGHT gene was shown to increase the risk of multiple sclerosis (MS) in a genome-wide association study (GWAS). Our aim was to investigate if serum levels of LIGHT were affected by this polymorphism and by the disease itself. Serum levels of LIGHT were investigated in four cohorts; 1) MS (n = 159) and controls (n = 160) in relation to rs1077667 genotype; 2) MS at relapse (n = 30) vs. healthy controls (n = 26); 3) MS (n = 27) vs. other neurological disease (OND, n = 33); and 4) MS patients before and after one year of treatment with natalizumab (n = 30). Carriers of the GG genotype had the lowest serum levels of LIGHT (p=0.02). Serum levels of LIGHT were increased in MS at relapse in two separate cohorts: vs. healthy controls (p=0.00005) and vs. remission (p=0.00006), other neurological disease (OND) (p=0.002) and OND with signs of inflammation (iOND; p=0.00005). Furthermore, serum levels of LIGHT were decreased by natalizumab treatment (p=0.001). Soluble LIGHT is an inhibitor of T-cell activation and GG carriers of rs1077667, with the highest risk for MS, had the lowest serum levels. The increased levels of LIGHT at times of increased MS activity suggest that soluble LIGHT is protective and may act to limit inflammation.Keywords
This publication has 24 references indexed in Scilit:
- Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosisNature, 2011
- Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosisNeurology, 2009
- Multiple sclerosisThe Lancet, 2008
- Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”Annals of Neurology, 2005
- Targeted Disruption of LIGHT Causes Defects in Costimulatory T Cell Activation and Reveals Cooperation with Lymphotoxin β in Mesenteric Lymph Node GenesisJournal of Experimental Medicine, 2002
- Reciprocal Expression of the TNF Family Receptor Herpes Virus Entry Mediator and Its Ligand LIGHT on Activated T Cells: LIGHT Down-Regulates Its Own ReceptorThe Journal of Immunology, 2000
- Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathwayNature Medicine, 2000
- LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer.Journal of Clinical Investigation, 1998
- LIGHT, a New Member of the TNF Superfamily, and Lymphotoxin α Are Ligands for Herpesvirus Entry MediatorImmunity, 1998
- New diagnostic criteria for multiple sclerosis: Guidelines for research protocolsAnnals of Neurology, 1983