{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:00:11Z","timestamp":1790226011342,"version":"4.1.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T00:00:00Z","timestamp":1561593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medical Research Council","award":["G0800629"],"award-info":[{"award-number":["G0800629"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rheumatol Int"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Primary Sj\u00f6gren\u2019s 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\u00f6gren\u2019s 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-\u03b3-induced protein-10 (IP-10), tumour necrosis factor-\u03b1 (TNF\u03b1), interferon-\u03b1 (IFN\u03b1), interferon-\u03b3 (IFN-\u03b3), and lymphotoxin-\u03b1 (LT-\u03b1) were significantly higher in patients with pSS (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009120) compared to non-fatigued controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200930). Levels of two proinflammatory cytokines, TNF-\u03b1 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.021) and LT-\u03b1 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.043), 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-\u03b1 and LT-\u03b1 have an inverse relationship with fatigue severity in pSS challenging the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions.\n                  <\/jats:p>","DOI":"10.1007\/s00296-019-04354-0","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T05:17:35Z","timestamp":1561612655000},"page":"1867-1873","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Fatigue in primary Sj\u00f6gren\u2019s syndrome (pSS) is associated with lower levels of proinflammatory cytokines: a validation study"],"prefix":"10.1007","volume":"39","author":[{"name":"UK Primary Sj\u00f6gren\u2019s Syndrome Registry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2246-9048","authenticated-orcid":false,"given":"Kristen","family":"Davies","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4856-1996","authenticated-orcid":false,"given":"Kamran","family":"Mirza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0083-8543","authenticated-orcid":false,"given":"Jessica","family":"Tarn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Howard-Tripp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9880-9948","authenticated-orcid":false,"given":"Simon J.","family":"Bowman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-5509","authenticated-orcid":false,"given":"Dennis","family":"Lendrem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5539-388X","authenticated-orcid":false,"given":"Wan-Fai","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,6,27]]},"reference":[{"issue":"1","key":"4354_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/BF03168931","volume":"171","author":"W Cullen","year":"2002","unstructured":"Cullen W, Kearney Y (2002) Bury G (2002) Prevalence of fatigue in general practice. 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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","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Patient and control samples were provided from the biobank of the United Kingdom Primary Sj\u04e7gren\u2019s Syndrome Registry (UKPSSR), which is funded by the Medical Research Council and based in Newcastle. Ethical approval for the use of human samples was granted by the North West Research Ethics Committee. The procedures used to analyse these samples followed were in accordance with the ethical standards of the North West Research Ethics Committee with the Helsinki Declaration 2013.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"Informed consent was gained from all patients and controls who have submitted their serum to the UKPSSR biobank for its use in research and for publication of its results.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}