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Fatigue in primary Sjögren’s syndrome (pSS) is associated with lower levels of proinflammatory cytokines: a validation study

Lookup NU author(s): Kristen Davies, Dr Kamran Mirza, Dr Jessica Tarn, Dr Nadia Howard-Tripp, Dr Dennis Lendrem, Professor Fai Ng

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease with symptoms including dryness, fatigue, and pain. The previous work by our group has suggested that certain proinflammatory cytokines are inversely related to patient-reported levels of fatigue. To date, these findings have not been validated. This study aims to validate this observation. Blood levels of seven cytokines were measured in 120 patients with pSS from the United Kingdom Primary Sjögren’s Syndrome Registry and 30 age-matched healthy non-fatigued controls. Patient-reported scores for fatigue were classified according to severity and compared to cytokine levels using analysis of variance. The differences between cytokines in cases and controls were evaluated using Wilcoxon test. A logistic regression model was used to determine the most important identifiers of fatigue. Five cytokines, interferon-γ-induced protein-10 (IP-10), tumour necrosis factor-α (TNFα), interferon-α (IFNα), interferon-γ (IFN-γ), and lymphotoxin-α (LT-α) were significantly higher in patients with pSS (n = 120) compared to non-fatigued controls (n = 30). Levels of two proinflammatory cytokines, TNF-α (p = 0.021) and LT-α (p = 0.043), were inversely related to patient-reported levels of fatigue. Cytokine levels, disease-specific and clinical parameters as well as pain, anxiety, and depression were used as predictors in our validation model. The model correctly identifies fatigue levels with 85% accuracy. Consistent with the original study, pain, depression, and proinflammatory cytokines appear to be the most powerful predictors of fatigue in pSS. TNF-α and LT-α have an inverse relationship with fatigue severity in pSS challenging the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions.


Publication metadata

Author(s): Davies K, Mirza K, Tarn J, Howard-Tripp N, Bowman SJ, Lendrem D, UK Primary Sjögren’s Syndrome Registry, Ng W-F

Publication type: Article

Publication status: Published

Journal: Rheumatology International

Year: 2019

Pages: ePub ahead of Print

Online publication date: 27/06/2019

Acceptance date: 18/06/2019

Date deposited: 08/07/2019

ISSN (print): 0172-8172

ISSN (electronic): 1437-160X

Publisher: Springer Berlin Heidelberg

URL: https://doi.org/10.1007/s00296-019-04354-0

DOI: 10.1007/s00296-019-04354-0


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