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Proinflammatory Adaptive Cytokine and Shed Tumor Necrosis Factor Receptor Levels Are Elevated Preceding Systemic Lupus Erythematosus Disease Flare
Author(s) -
Munroe Melissa E.,
Vista Evan S.,
Guthridge Joel M.,
Thompson Linda F.,
Merrill Joan T.,
James Judith A.
Publication year - 2014
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38573
Subject(s) - proinflammatory cytokine , medicine , immunology , tumor necrosis factor alpha , cytokine , disease , immune system , b cell activating factor , inflammation , antibody , b cell
Objective Systemic lupus erythematosus (SLE) is a multifaceted disease characterized by immune dysregulation and unpredictable disease activity. This study sought to evaluate the changes in plasma concentrations of soluble mediators that precede clinically defined disease flares. Methods Fifty‐two different soluble mediators, including cytokines, chemokines, and soluble receptors, were examined using validated multiplex bead‐based or enzyme‐linked immunosorbent assays in plasma from 28 European American patients with SLE who developed disease flare 6 or 12 weeks after a baseline assessment (preflare), 28 matched SLE patients without impending flare (nonflare), and 28 matched healthy controls. In a subset of 13 SLE patients, mediators within samples obtained preceding disease flare were compared with those within samples from the same individual obtained during a clinically stable period without flare. Results Compared to SLE patients with clinically stable disease, SLE patients with impending flare had significant alterations ( P ≤ 0.01) in the levels of 27 soluble mediators at baseline; specifically, the levels of proinflammatory mediators, including Th1‐, Th2‐, and Th17‐type cytokines, were significantly higher several weeks before clinical flare. Baseline levels of regulatory cytokines, including interleukin‐10 and transforming growth factor β, were higher in nonflare SLE patients, whereas baseline levels of soluble tumor necrosis factor receptor type I (TNFRI), TNFRII, Fas, FasL, and CD40L were significantly higher ( P ≤ 0.002) in preflare SLE patients. The normalized and weighted combined soluble mediator score was significantly higher ( P ≤ 0.0002) in preflare samples from SLE patients compared to samples from the same patients obtained during periods of stable disease. Conclusion The levels of proinflammatory adaptive cytokines and shed TNF receptors are elevated prior to disease flare, while the levels of regulatory mediators are elevated during periods of stable disease. Alterations in the balance between inflammatory and regulatory mediators may help identify patients at risk of disease flare and help decipher the pathogenic mechanisms of SLE.