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Lookup NU author(s): Dr Jessica Tarn, Andini Natasari, Colin Gillespie, Sheryl Mitchell, Dr Katie Hackett, Dr Vadivelu Saravanan, Dr David Coady, Dr Steven Young-Min, Dr Bridget Griffiths, Dr Dennis LendremORCiD, Professor Fai NgORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Objectives: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS). Methods: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels. Results: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines - interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α ( p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022) - were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy. Conclusions: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.
Author(s): Tripp NH, Tarn J, Natasari A, Gillespie C, Mitchell S, Hackett KL, Bowman SJ, Price E, Pease CT, Emery P, Lanyon P, Hunter J, Gupta M, Bombardieri M, Sutcliffe N, Pitzalis C, McLaren J, Cooper A, Regan M, Giles I, Isenberg DA, Saravanan V, Coady D, Dasgupta B, McHugh N, Young-Min S, Moots R, Gendi N, Akil M, Griffiths B, Lendrem DW, Ng W-F
Publication type: Article
Publication status: Published
Journal: RMD Open
Year: 2016
Volume: 2
Print publication date: 01/07/2016
Online publication date: 19/07/2016
Acceptance date: 24/06/2016
Date deposited: 03/05/2017
ISSN (electronic): 2056-5933
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/rmdopen-2016-000282
DOI: 10.1136/rmdopen-2016-000282
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