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. 2019 Nov;39(11):1867-1873.
doi: 10.1007/s00296-019-04354-0. Epub 2019 Jun 27.

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

Kristen Davies  1 , Kamran Mirza  2 , Jessica Tarn  2 , Nadia Howard-Tripp  3 , Simon J Bowman  4 , Dennis Lendrem  2   3   5 ; UK Primary Sjögren’s Syndrome Registry; Wan-Fai Ng  2   3   5
Collaborators, Affiliations

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

Kristen Davies et al. Rheumatol Int. 2019 Nov.

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.

Keywords: Cytokines; Fatigue; Primary Sjögren’s syndrome; Proinflammatory.

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Conflict of interest statement

K. Davies declares that he has no conflicts of interest. K. Mirza declares that he has no conflicts of interest. J. Tarn declares that she has no conflicts of interest. N. Howard-Tripp declares that she has no conflicts of interest. S J Bowman declares that he has no conflicts of interest. D. Lendrem declares that he has no conflicts of interest. W.-F. Ng declares that he has no conflicts of interest

Figures

Fig. 1
Fig. 1
a Table of proinflammatory cytokine levels in patients with pSS. Values in the table represent median and 25th, 75th centile (pmol/L). Bold typeface indicates statistical significance of cytokine serum level between fatigue groups as determined by ANOVA. b Proinflammatory cytokine levels in patients with pSS. Values in the table represent median and 25th, 75th centile (pmol/L). Bold typeface indicates statistical significance of cytokine serum level between fatigue groups as determined by ANOVA
Fig. 2
Fig. 2
Observed and predicted fatigue levels for the ordinal logistic regression model with all seven cytokines, WCC, lymphocytes, neutrophils, ESR, CRP, ESSDAI scores, dryness scores, depression, pain, and anxiety. This full model predicts fatigue level correctly in 85% of cases
See this image and copyright information in PMC

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