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

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Rheumatol Int. 2019 Jun 27. doi: 10.1007/s00296-019-04354-0. [Epub ahead of print]
Fatigue in primary Sjögren's syndrome (pSS) is associated with lower levels of proinflammatory cytokines: a validation study.
Davies K1, Mirza K2, Tarn J2, Howard-Tripp N3, Bowman SJ4, Lendrem D2,3,5; UK Primary Sjögren’s Syndrome Registry, Ng WF2,3,5.
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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
PMID: 31250166 DOI: 10.1007/s00296-019-04354-0
 
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This is a weird but cool study.

If you have Sjogrens you have higher cytokines (signalling molecules). But if you have Sjogrens and your cytokines are low you'll end up feeling more fatigued!

So the cytolkines seem to be working to protect people and it's not so simple as saying the high cytokines are causing the symptoms. Turns out we have a lot to learn about cytokines.

Here's the data tables from the study. Table A is controls vs patients. Patients have higher cytokines in six of the seven cytokines measures. Table B splits patients up into groups depending on how severe their fatigue is, and for two of the seven cytokines, the patterns appears to reverse! People who *feel* healthier, have higher cytokines!
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pattismith

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cytokine signature might correlate with lymphocytes and NK cells profile;
A pity they didn't investigate the immune cells profile of their patients, we could have find some common pathway between Sjogren fatigue and ME/CFS (or not)!
It would be valuable as well to look for correlation with anti-Ro (SSA) and anti-La (SSB) antibodies and for anti-M3R antibodies.