TY - JOUR
T1 - Fatigue in primary Sjögren’s syndrome (pSS) is associated with lower levels of proinflammatory cytokines
T2 - a validation study
AU - UK Primary Sjögren’s Syndrome registry
AU - Davies, Kristen
AU - Mirza, Kamran
AU - Tarn, Jessica
AU - Howard-Tripp, Nadia
AU - Bowman, Simon J.
AU - Lendrem, Dennis
AU - Hall, Frances
AU - Bacabac, Elalaine C.
AU - Frankland, Helen
AU - Moots, Robert
AU - Chadravarty, Kuntal
AU - Lamabadusuriya, Shamin
AU - Bombardieri, Michele
AU - Pitzalis, Constantino
AU - Sutcliffe, Nurhan
AU - Breston, Celia
AU - Gendi, Nagui
AU - Culfear, Karen
AU - Riddell, Claire
AU - Hamburger, John
AU - Richards, Andrea
AU - Rauz, Saaeha
AU - Brailsford, Sue
AU - Dasgin, Joanne
AU - Logan, Joanne
AU - Mulherin, Diarmuid
AU - Andrews, Jacqueline
AU - Emery, Paul
AU - McManus, Alison
AU - Pease, Colin
AU - Pickles, David
AU - Booth, Alison
AU - Regan, Marian
AU - King, Jon
AU - Holt, Amanda
AU - Dimitroulas, Theodoros
AU - Kadiki, Lucy
AU - Kaur, Daljit
AU - Kitas, George
AU - Khan, Abdul
AU - Cosier, Tracey
AU - Panthakalam, null
AU - Mintrim, Kelly
AU - Lloyd, Mark
AU - Moore, Lisa
AU - Gordon, Esther
AU - Lawson, Cathy
AU - Gupta, Monica
AU - McHugh, Neil
AU - Pauling, John
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - Cytokines
KW - Fatigue
KW - Primary Sjögren’s syndrome
KW - Proinflammatory
UR - http://www.scopus.com/inward/record.url?scp=85068212982&partnerID=8YFLogxK
U2 - 10.1007/s00296-019-04354-0
DO - 10.1007/s00296-019-04354-0
M3 - Article
C2 - 31250166
AN - SCOPUS:85068212982
SN - 0172-8172
VL - 39
SP - 1867
EP - 1873
JO - Rheumatology International
JF - Rheumatology International
IS - 11
ER -