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2014 ; 66
(7
): 1888-99
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Proinflammatory adaptive cytokine and shed tumor necrosis factor receptor levels
are elevated preceding systemic lupus erythematosus disease flare
#MMPMID24578190
Munroe ME
; Vista ES
; Guthridge JM
; Thompson LF
; Merrill JT
; James JA
Arthritis Rheumatol
2014[Jul]; 66
(7
): 1888-99
PMID24578190
show ga
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 ?, 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.