BACKGROUND: Recently, a polymorphism in the LIGHT gene was shown to increase the risk of multiple sclerosis (MS) in a genome-wide association study (GWAS). OBJECTIVE: Our aim was to investigate if serum levels of LIGHT were affected by this polymorphism and by the disease itself. METHODS: 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). RESULTS: 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). CONCLUSION: 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.
BACKGROUND: Recently, a polymorphism in the LIGHT gene was shown to increase the risk of multiple sclerosis (MS) in a genome-wide association study (GWAS). OBJECTIVE: Our aim was to investigate if serum levels of LIGHT were affected by this polymorphism and by the disease itself. METHODS: 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). RESULTS: 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). CONCLUSION: 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.
Authors: Ashley H Beecham; Nikolaos A Patsopoulos; Dionysia K Xifara; Mary F Davis; Anu Kemppinen; Chris Cotsapas; Tejas S Shah; Chris Spencer; David Booth; An Goris; Annette Oturai; Janna Saarela; Bertrand Fontaine; Bernhard Hemmer; Claes Martin; Frauke Zipp; Sandra D'Alfonso; Filippo Martinelli-Boneschi; Bruce Taylor; Hanne F Harbo; Ingrid Kockum; Jan Hillert; Tomas Olsson; Maria Ban; Jorge R Oksenberg; Rogier Hintzen; Lisa F Barcellos; Cristina Agliardi; Lars Alfredsson; Mehdi Alizadeh; Carl Anderson; Robert Andrews; Helle Bach Søndergaard; Amie Baker; Gavin Band; Sergio E Baranzini; Nadia Barizzone; Jeffrey Barrett; Céline Bellenguez; Laura Bergamaschi; Luisa Bernardinelli; Achim Berthele; Viola Biberacher; Thomas M C Binder; Hannah Blackburn; Izaura L Bomfim; Paola Brambilla; Simon Broadley; Bruno Brochet; Lou Brundin; Dorothea Buck; Helmut Butzkueven; Stacy J Caillier; William Camu; Wassila Carpentier; Paola Cavalla; Elisabeth G Celius; Irène Coman; Giancarlo Comi; Lucia Corrado; Leentje Cosemans; Isabelle Cournu-Rebeix; Bruce A C Cree; Daniele Cusi; Vincent Damotte; Gilles Defer; Silvia R Delgado; Panos Deloukas; Alessia di Sapio; Alexander T Dilthey; Peter Donnelly; Bénédicte Dubois; Martin Duddy; Sarah Edkins; Irina Elovaara; Federica Esposito; Nikos Evangelou; Barnaby Fiddes; Judith Field; Andre Franke; Colin Freeman; Irene Y Frohlich; Daniela Galimberti; Christian Gieger; Pierre-Antoine Gourraud; Christiane Graetz; Andrew Graham; Verena Grummel; Clara Guaschino; Athena Hadjixenofontos; Hakon Hakonarson; Christopher Halfpenny; Gillian Hall; Per Hall; Anders Hamsten; James Harley; Timothy Harrower; Clive Hawkins; Garrett Hellenthal; Charles Hillier; Jeremy Hobart; Muni Hoshi; Sarah E Hunt; Maja Jagodic; Ilijas Jelčić; Angela Jochim; Brian Kendall; Allan Kermode; Trevor Kilpatrick; Keijo Koivisto; Ioanna Konidari; Thomas Korn; Helena Kronsbein; Cordelia Langford; Malin Larsson; Mark Lathrop; Christine Lebrun-Frenay; Jeannette Lechner-Scott; Michelle H Lee; Maurizio A Leone; Virpi Leppä; Giuseppe Liberatore; Benedicte A Lie; Christina M Lill; Magdalena Lindén; Jenny Link; Felix Luessi; Jan Lycke; Fabio Macciardi; Satu Männistö; Clara P Manrique; Roland Martin; Vittorio Martinelli; Deborah Mason; Gordon Mazibrada; Cristin McCabe; Inger-Lise Mero; Julia Mescheriakova; Loukas Moutsianas; Kjell-Morten Myhr; Guy Nagels; Richard Nicholas; Petra Nilsson; Fredrik Piehl; Matti Pirinen; Siân E Price; Hong Quach; Mauri Reunanen; Wim Robberecht; Neil P Robertson; Mariaemma Rodegher; David Rog; Marco Salvetti; Nathalie C Schnetz-Boutaud; Finn Sellebjerg; Rebecca C Selter; Catherine Schaefer; Sandip Shaunak; Ling Shen; Simon Shields; Volker Siffrin; Mark Slee; Per Soelberg Sorensen; Melissa Sorosina; Mireia Sospedra; Anne Spurkland; Amy Strange; Emilie Sundqvist; Vincent Thijs; John Thorpe; Anna Ticca; Pentti Tienari; Cornelia van Duijn; Elizabeth M Visser; Steve Vucic; Helga Westerlind; James S Wiley; Alastair Wilkins; James F Wilson; Juliane Winkelmann; John Zajicek; Eva Zindler; Jonathan L Haines; Margaret A Pericak-Vance; Adrian J Ivinson; Graeme Stewart; David Hafler; Stephen L Hauser; Alastair Compston; Gil McVean; Philip De Jager; Stephen J Sawcer; Jacob L McCauley Journal: Nat Genet Date: 2013-09-29 Impact factor: 38.330
Authors: Madhan Thamilarasan; Michael Hecker; Robert Hermann Goertsches; Brigitte Katrin Paap; Ina Schröder; Dirk Koczan; Hans-Jürgen Thiesen; Uwe Klaus Zettl Journal: J Neuroinflammation Date: 2013-10-17 Impact factor: 8.322
Authors: Arianne C Richard; James E Peters; James C Lee; Golnaz Vahedi; Alejandro A Schäffer; Richard M Siegel; Paul A Lyons; Kenneth G C Smith Journal: Genome Med Date: 2016-07-19 Impact factor: 11.117