Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines

Nadia Howard Tripp; Jessica Tarn; Andini Natasari; Colin Gillespie; Sheryl Mitchell; Katie L Hackett; Simon J Bowman; Elizabeth Price; Colin T Pease; Paul Emery; Peter Lanyon; John Hunter; Monica Gupta; Michele Bombardieri; Nurhan Sutcliffe; Costantino Pitzalis; John McLaren; Annie Cooper; Marian Regan; Ian Giles; David A Isenberg; Vadivelu Saravanan; David Coady; Bhaskar Dasgupta; Neil McHugh; Steven Young-Min; Robert Moots; Nagui Gendi; Mohammed Akil; Bridget Griffiths; Dennis W Lendrem; Wan-Fai Ng

doi:10.1136/rmdopen-2016-000282

Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines

Nadia Howard Tripp, Jessica Tarn, Andini Natasari, Colin Gillespie, Sheryl Mitchell, Katie L Hackett, Simon J Bowman, Elizabeth Price, Colin T Pease, Paul Emery, Peter Lanyon, John Hunter, Monica Gupta, Michele Bombardieri, Nurhan Sutcliffe, Costantino Pitzalis, John McLaren, Annie Cooper, Marian Regan, Ian GilesDavid A Isenberg, Vadivelu Saravanan, David Coady, Bhaskar Dasgupta, Neil McHugh, Steven Young-Min, Robert Moots, Nagui Gendi, Mohammed Akil, Bridget Griffiths, Dennis W Lendrem, Wan-Fai Ng

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Abstract

OBJECTIVES: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).

METHODS: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.

RESULTS: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines-interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)-were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.

CONCLUSIONS: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

Original language	English
Pages (from-to)	e000282
Journal	BMJ Open
Volume	2
Issue number	2
DOIs	https://doi.org/10.1136/rmdopen-2016-000282
Publication status	Published - 19 Jul 2016

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http://dx.doi.org/10.1136/rmdopen-2016-000282Licence: CC BY

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Howard Tripp, N., Tarn, J., Natasari, A., Gillespie, C., Mitchell, S., Hackett, K. L., Bowman, S. J., Price, E., Pease, C. T., Emery, P., Lanyon, P., Hunter, J., Gupta, M., Bombardieri, M., Sutcliffe, N., Pitzalis, C., McLaren, J., Cooper, A., Regan, M., ... Ng, W.-F. (2016). Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines. BMJ Open, 2(2), e000282. https://doi.org/10.1136/rmdopen-2016-000282

Howard Tripp, N, Tarn, J, Natasari, A, Gillespie, C, Mitchell, S, Hackett, KL, Bowman, SJ, Price, E, Pease, CT, Emery, P, Lanyon, P, Hunter, J, Gupta, M, Bombardieri, M, Sutcliffe, N, Pitzalis, C, McLaren, J, Cooper, A, Regan, M, Giles, I, Isenberg, DA, Saravanan, V, Coady, D, Dasgupta, B, McHugh, N, Young-Min, S, Moots, R, Gendi, N, Akil, M, Griffiths, B, Lendrem, DW & Ng, W-F 2016, 'Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines', BMJ Open, vol. 2, no. 2, pp. e000282. https://doi.org/10.1136/rmdopen-2016-000282

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title = "Fatigue in primary Sj{\"o}gren's syndrome is associated with lower levels of proinflammatory cytokines",

abstract = "OBJECTIVES: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sj{\"o}gren's syndrome (pSS).METHODS: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sj{\"o}gren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.RESULTS: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines-interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)-were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.CONCLUSIONS: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.",

author = "{Howard Tripp}, Nadia and Jessica Tarn and Andini Natasari and Colin Gillespie and Sheryl Mitchell and Hackett, {Katie L} and Bowman, {Simon J} and Elizabeth Price and Pease, {Colin T} and Paul Emery and Peter Lanyon and John Hunter and Monica Gupta and Michele Bombardieri and Nurhan Sutcliffe and Costantino Pitzalis and John McLaren and Annie Cooper and Marian Regan and Ian Giles and Isenberg, {David A} and Vadivelu Saravanan and David Coady and Bhaskar Dasgupta and Neil McHugh and Steven Young-Min and Robert Moots and Nagui Gendi and Mohammed Akil and Bridget Griffiths and Lendrem, {Dennis W} and Wan-Fai Ng",

year = "2016",

month = jul,

day = "19",

doi = "10.1136/rmdopen-2016-000282",

language = "English",

volume = "2",

pages = "e000282",

journal = "BMJ Open",

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number = "2",

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TY - JOUR

T1 - Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines

AU - Howard Tripp, Nadia

AU - Tarn, Jessica

AU - Natasari, Andini

AU - Gillespie, Colin

AU - Mitchell, Sheryl

AU - Hackett, Katie L

AU - Bowman, Simon J

AU - Price, Elizabeth

AU - Pease, Colin T

AU - Emery, Paul

AU - Lanyon, Peter

AU - Hunter, John

AU - Gupta, Monica

AU - Bombardieri, Michele

AU - Sutcliffe, Nurhan

AU - Pitzalis, Costantino

AU - McLaren, John

AU - Cooper, Annie

AU - Regan, Marian

AU - Giles, Ian

AU - Isenberg, David A

AU - Saravanan, Vadivelu

AU - Coady, David

AU - Dasgupta, Bhaskar

AU - McHugh, Neil

AU - Young-Min, Steven

AU - Moots, Robert

AU - Gendi, Nagui

AU - Akil, Mohammed

AU - Griffiths, Bridget

AU - Lendrem, Dennis W

AU - Ng, Wan-Fai

PY - 2016/7/19

Y1 - 2016/7/19

N2 - OBJECTIVES: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).METHODS: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.RESULTS: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines-interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)-were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.CONCLUSIONS: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

AB - OBJECTIVES: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).METHODS: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.RESULTS: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines-interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)-were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.CONCLUSIONS: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

UR - http://dx.doi.org/10.1136/rmdopen-2016-000282

U2 - 10.1136/rmdopen-2016-000282

DO - 10.1136/rmdopen-2016-000282

M3 - Article

C2 - 27493792

SN - 2044-6055

VL - 2

SP - e000282

JO - BMJ Open

JF - BMJ Open

IS - 2

ER -

Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines

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