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

a validation study

UK Primary Sjögren’s Syndrome registry

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)1867-1873
Number of pages7
JournalRheumatology International
Volume39
Issue number11
Early online date27 Jun 2019
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • Cytokines
  • Fatigue
  • Primary Sjögren’s syndrome
  • Proinflammatory

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Fatigue in primary Sjögren’s syndrome (pSS) is associated with lower levels of proinflammatory cytokines : a validation study. / UK Primary Sjögren’s Syndrome registry.

In: Rheumatology International, Vol. 39, No. 11, 01.11.2019, p. 1867-1873.

Research output: Contribution to journalArticle

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abstract = "Primary Sj{\"o}gren’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 Sj{\"o}gren’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.",
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author = "{UK Primary Sj{\"o}gren’s Syndrome registry} and Kristen Davies and Kamran Mirza and Jessica Tarn and Nadia Howard-Tripp and Bowman, {Simon J.} and Dennis Lendrem and Frances Hall and Bacabac, {Elalaine C.} and Helen Frankland and Robert Moots and Kuntal Chadravarty and Shamin Lamabadusuriya and Michele Bombardieri and Constantino Pitzalis and Nurhan Sutcliffe and Celia Breston and Nagui Gendi and Karen Culfear and Claire Riddell and John Hamburger and Andrea Richards and Saaeha Rauz and Sue Brailsford and Joanne Dasgin and Joanne Logan and Diarmuid Mulherin and Jacqueline Andrews and Paul Emery and Alison McManus and Colin Pease and David Pickles and Alison Booth and Marian Regan and Jon King and Amanda Holt and Theodoros Dimitroulas and Lucy Kadiki and Daljit Kaur and George Kitas and Abdul Khan and Tracey Cosier and Panthakalam and Kelly Mintrim and Mark Lloyd and Lisa Moore and Esther Gordon and Cathy Lawson and Monica Gupta and Neil McHugh and John Pauling",
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