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Abstract Number: 565

Fatigue in Primary Sjögren’s Syndrome (pSS) Is Associated with Lower Levels of Proinflammatory Cytokines: A Validation Study

Kristen Davies1, Kamran Mirza1, Jessica Tarn2, Nadia Howard Tripp3, Robert J. Moots4, Nagui Gendi5, Michele Bombardieri6, Costantino Pitzalis6, Nurhan Sutcliffe6, Simon Bowman7, Neil J. McHugh8, John McLaren9, Devesh Mewar10, David Coady11, Kirsten MacKay12, Susan Knight13, Monica Gupta14, Marian Regan15, Cathy Lawson16, Jacqueline Andrews17, Peter Lanyon18, Mohammed Akil19, Elizabeth Price20, Annie Cooper21, Frances Hall22, Theodoros Dimitroulas23, Gavin Clunie24, Saravanan Vadivelu25, Ian Giles26, Bhaskar Dasgupta27, Steve Young-Min28, Dennis Lendrem29,30 and Wan-Fai Ng2,31, 1Institute of Cellular Medicine, Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK, Newcastle-Upon-Tyne, United Kingdom, 2Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK, Newcastle-Upon-Tyne, United Kingdom, 3Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK, Newcastle-upon-Tyne, United Kingdom, 4University of Liverpool, Liverpool, UK, Liverpool, United Kingdom, 5Basildon and Thurrock University Hospital, Basildon, UK, Basildon, United Kingdom, 6Barts Health NHS Trust & Barts and the London School of Medicine & Dentistry, London, UK, London, United Kingdom, 7Department of Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, Birmingham, United Kingdom, 8Royal National Hospital for Rheumatic Diseases, Bath, UK, Bath, United Kingdom, 9NHS Fife, Kirkcaldy, UK, Kirkcaldy, United Kingdom, 10Royal Liverpool University Hospital, Liverpool, UK, Liverpool, United Kingdom, 11Sunderland Royal Hospital, Sunderland, UK, Sunderland, United Kingdom, 12Torbay Hospital, Torquay, UK, Torquay, United Kingdom, 13Macclesfield General Hospital, Macclesfield, UK, macclesfield, United Kingdom, 14Gartnavel General Hospital, Glasgow, UK, Glasgow, United Kingdom, 15Royal Derby Hospital, Derby, UK, Derby, United Kingdom, 16Harrogate District Hospital, Harrogate, UK, Harrogate, United Kingdom, 17Leeds Teaching Hospitals NHS Trust, Leeds, UK, Leeds, United Kingdom, 18Nottingham University Hospitals NHS Trust, Nottingham, UK, Nottingham, United Kingdom, 19Royal Hallamshire Hospital, Sheffield, UK, Sheffield, United Kingdom, 20Great Western Hospital, Swindon, UK, Swindon, United Kingdom, 21Royal Hampshire County Hospital, Winchester, UK, Winchester, United Kingdom, 22Addenbrooke’s Hospital, Cambridge, UK, Cambridge, United Kingdom, 23Dudley Group of Hospitals NHS Foundation Trust, Dudley, UK, Dudley, United Kingdom, 24Ipswich Hospital NHS Trust, Ipswich, UK, Ipswich, United Kingdom, 25Queen Elizabeth Hospital, Gateshead, UK, Gateshead, United Kingdom, 26Centre for Rheumatology, University College London, Centre for Rheumatology, University College London, UK, London, United Kingdom, 27Rheumatology, Southend University Hospital NHS Foundation Trust, Southend, UK, Westcliff-on-Sea, United Kingdom, 28Queen Alexander Hospital, Portsmouth, UK, Portsmouth, United Kingdom, 29Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK, Newcastle, United Kingdom, 30Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK, Newcastle-upon-Tyne, United Kingdom, 31Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle-upon-Tyne, UK, Newcastle-Upon-Tyne, United Kingdom

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: cytokines, dry eyes, fatigue and pain, Sjogren's syndrome

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Session Information

Date: Sunday, November 5, 2017

Title: Sjögren's Syndrome Poster I: Translational Research

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Primary Sjögren’s syndrome (pSS) is a chronic autoimmune rheumatic disease causing various symptoms including dryness, fatigue and pain. Previous work by our group has suggested that certain pro-inflammatory cytokines are inversely related to patient-reported levels of fatigue. This model in that study using pro-inflammatory cytokine levels, disease-specific and clinical parameters was able to predict fatigue with 67% accuracy. To date, these findings have not been validated. This study aims to validate this observation.

Methods: 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 predictors of fatigue.

Results: Three cytokines, interferon-γ-induced protein-10 (IP-10), tumour necrosis factor-α (TNFα) and interferon-α (IFNα) were significantly higher in patients with pSS (n=120) compared to non-fatigued controls (n=30). Levels of two pro-inflammatory cytokines, TNF-α (p=0.021) and lymphotoxin-α (p=0.043), were inversely related to patient-reported levels of fatigue. Based on the model previous used a regression model was created to predict fatigue in pSS. Cytokine levels, disease-specific and clinical parameters as well as pain, anxiety and depression were used as predictors in this validation model. The model correctly predicts fatigue levels with 85% accuracy.

Conclusion: Depression, pain and proinflammatory cytokines appear to be the most powerful predictors of fatigue in pSS, which is consistent with the original study. This data further challenges the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Validation in an independent international cohort would be necessary to further confirm these results.

Figure 1: Box plot showing median cytokine levels and IQR for a) IP-10, b) TNF-α, c) LT-α and d) IFN-γ in controls and pSS fatigue groups.

Figure 2: (A) Full ordinal logistic regression model with all parameters. All of these variables predict fatigue correct in 85% of cases. (B) shows that IFN-γ, IP-10, depression and pain alone predicted fatigue level with 80% accuracy.

 


Disclosure: K. Davies, None; K. Mirza, None; J. Tarn, None; N. Howard Tripp, None; R. J. Moots, None; N. Gendi, None; M. Bombardieri, GSK, Amgen/MedImmune and UCB, 5; C. Pitzalis, None; N. Sutcliffe, None; S. Bowman, I have consulted in the field of Sjogren's for: AstraZeneca/Meddimmune, BMS, Celgene, Eli Lilly, Glenmark, GSK, MTPharma, Novartis, Ono, Takeda, UCB, xtlbio). Roche provided Rituximab for the TRACTISS Study, 5; N. J. McHugh, None; J. McLaren, None; D. Mewar, None; D. Coady, None; K. MacKay, None; S. Knight, None; M. Gupta, None; M. Regan, None; C. Lawson, None; J. Andrews, None; P. Lanyon, None; M. Akil, None; E. Price, None; A. Cooper, None; F. Hall, None; T. Dimitroulas, None; G. Clunie, None; S. Vadivelu, None; I. Giles, None; B. Dasgupta, None; S. Young-Min, None; D. Lendrem, None; W. F. Ng, None.

To cite this abstract in AMA style:

Davies K, Mirza K, Tarn J, Howard Tripp N, Moots RJ, Gendi N, Bombardieri M, Pitzalis C, Sutcliffe N, Bowman S, McHugh NJ, McLaren J, Mewar D, Coady D, MacKay K, Knight S, Gupta M, Regan M, Lawson C, Andrews J, Lanyon P, Akil M, Price E, Cooper A, Hall F, Dimitroulas T, Clunie G, Vadivelu S, Giles I, Dasgupta B, Young-Min S, Lendrem D, Ng WF. Fatigue in Primary Sjögren’s Syndrome (pSS) Is Associated with Lower Levels of Proinflammatory Cytokines: A Validation Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/fatigue-in-primary-sjogrens-syndrome-pss-is-associated-with-lower-levels-of-proinflammatory-cytokines-a-validation-study/. Accessed .
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