Simpson Jr, S and Stewart, N and van der Mei, I and Otahal, P and Charlesworth, J and Ponsonby, AL and Blizzard, L and Dwyer, T and Pittas, F and Gies, P and Taylor, B, Stimulated PBMC-produced IFN-γ and TNF-α are associated with altered relapse risk in multiple sclerosis: Results from a prospective cohort study, Journal of Neurology, Neurosurgery and Psychiatry, 86 pp. 200-207. ISSN 0022-3050 (2015) [Refereed Article]
Copyright 2014 BMJ Publishing Group
Methods: Cytokine production from PBMCs taken in summer and winter was measured by ELISA. Predictors of cytokines assessed by multilevel mixed-effects linear regression. Predictors of relapse assessed by survival analysis.
Results: Increasing IFN-γ was associated with increasing relapse risk, while increasing TNF-α reduced relapse risk after adjusting for IFN-γ. IL-10 and IL4 were not consistently associated with relapse risk. IFN-γ's effects on relapse were greatly attenuated by immunomodulatory therapies, by summer season and by higher serum vitamin D, whereas TNF-α's inverse association with relapse was only present in these circumstances. The TNF-α inverse association with relapse was only present among persons carrying the wild-type of the functional SNP rs1800693 in TNFRSF1A that has been previously associated with MS risk.
Conclusions: We found strong effects of IFN-γ and TNF-α on relapse risk, these differing by immunomodulatory therapy, season, and serum vitamin D, as well as by genotype. These results indicate altered reactivity of immune cells modulate MS disease.
|Item Type:||Refereed Article|
|Research Division:||Medical and Health Sciences|
|Research Field:||Central Nervous System|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Nervous System and Disorders|
|Author:||Simpson Jr, S (Dr Steve Simpson JR)|
|Author:||Stewart, N (Dr Niall Stewart)|
|Author:||van der Mei, I (Associate Professor Ingrid van der Mei)|
|Author:||Otahal, P (Mr Petr Otahal)|
|Author:||Charlesworth, J (Dr Jac Charlesworth)|
|Author:||Blizzard, L (Associate Professor Leigh Blizzard)|
|Author:||Pittas, F (Dr Fotini Pittas)|
|Author:||Taylor, B (Professor Bruce Taylor)|
|Year Published:||2015 (online first 2014)|
|Web of Science® Times Cited:||6|
|Deposited By:||Menzies Institute for Medical Research|
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