A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis

John Manley III Davis, Keith L Knutson, Michael A. Strausbauch, Cynthia Crowson, Terry M Therneau, Peter J. Wettstein, Veronique Lee Roger, Eric Lawrence Matteson, Sherine E. Gabriel

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22 Citations (Scopus)

Abstract

Objective Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo. Methods RA patients (n = 212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates. Results An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95% confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors. Conclusion The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.

Original languageEnglish (US)
Pages (from-to)1497-1506
Number of pages10
JournalArthritis and Rheumatism
Volume63
Issue number6
DOIs
StatePublished - Jun 2011

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Left Ventricular Dysfunction
Rheumatoid Arthritis
Logistic Models
Cytokines
Brain Natriuretic Peptide
Immunoassay
Glucocorticoids
Longitudinal Studies
Echocardiography
Cause of Death
Immune System
Interleukin-6
Blood Cells
Fibrosis
Heart Failure
Odds Ratio
Confidence Intervals
Wounds and Injuries
Serum

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

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title = "A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis",
abstract = "Objective Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo. Methods RA patients (n = 212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates. Results An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95{\%} confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors. Conclusion The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.",
author = "Davis, {John Manley III} and Knutson, {Keith L} and Strausbauch, {Michael A.} and Cynthia Crowson and Therneau, {Terry M} and Wettstein, {Peter J.} and Roger, {Veronique Lee} and Matteson, {Eric Lawrence} and Gabriel, {Sherine E.}",
year = "2011",
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T1 - A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis

AU - Davis, John Manley III

AU - Knutson, Keith L

AU - Strausbauch, Michael A.

AU - Crowson, Cynthia

AU - Therneau, Terry M

AU - Wettstein, Peter J.

AU - Roger, Veronique Lee

AU - Matteson, Eric Lawrence

AU - Gabriel, Sherine E.

PY - 2011/6

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N2 - Objective Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo. Methods RA patients (n = 212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates. Results An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95% confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors. Conclusion The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.

AB - Objective Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo. Methods RA patients (n = 212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates. Results An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95% confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors. Conclusion The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.

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