Proinflammatory Adaptive Cytokine and Shed Tumor Necrosis Factor Receptor Levels Are Elevated Preceding Systemic Lupus Erythematosus Disease Flare

Abstract

Objective Systemic lupus erythematosus (SLE) is a multifaceted disease characterized by immune dysregulation and unpredictable disease activity. This study evaluated changes in plasma concentrations of soluble mediators preceding clinically-defined disease flares. Methods Soluble mediators (n=52) were examined, including cytokines, chemokines, and soluble receptors, using validated multiplex bead-based or enzyme-linked immunosorbent assays in plasma from European American SLE patients who developed disease flare 6 or 12 weeks after baseline assessment were compared to 28 matched SLE patients without impending flare and 28 matched healthy controls (n=84). For a subset, mediators within samples preceding SLE disease flare and during a clinically stable period from the same individual were compared. Results Compared to clinically stable patients, patients with impending flare had significant (p≤0.01) alterations in 27 soluble mediators at baseline with significantly higher levels of pro-inflammatory mediators, including Th1, Th2, and Th17-type cytokines, several weeks before clinical flare. Baseline levels of regulatory cytokines, including IL-10 and TGF-β, were higher in non-flare SLE patients, while baseline levels of soluble TNFRI, TNFRII, Fas, FasL, and CD40L were significantly greater in pre-flare patients (p≤0.002). A normalized and weighted combined soluble mediator score was significantly higher in pre-flare SLE patients versus those with stable disease (p≤0.0002). Conclusion Pro-inflammatory adaptive cytokines and shed TNF receptors, are elevated prior to disease flare, while 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 SLE pathogenic mechanisms.

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

“…These findings support the idea that alterations in the balance between inflammatory and regulatory mediators may help identify patients at risk of disease flare and help decipher SLE pathogenic mechanisms [84]. Concerning the role of regulatory T cells in SLE, most studies point to a reduction in Treg cell number and function in SLE [85][86][87].…”

“…Recently, an interesting study evaluated changes in plasma concentrations of soluble mediators preceding clinically-defined disease flares in SLE. They found that patients with impending flare had significant alterations in a wide variety of soluble mediators at baseline with significantly higher levels of pro-inflammatory mediators, including Th1, Th2, and Th17-type cytokines, several weeks before clinical flare compared to clinically stable patients [84]. Levels of regulatory cytokines, including IL-10…”

iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling

“…Peripheral blood mononuclear cells (PBMCs) of SLE patients show increased Adam17 expression (9). Soluble shedding substrates of ADAM17 have been found in the plasma and urine of lupus mice and SLE patients, and some of these soluble factors are elevated prior to flare (10)(11)(12). Among these, 2 major ADAM17 substrates, TNF-α and heparin-binding EGF (HB-EGF) (7,8), have been separately implicated as important mediators of kidney damage in lupus (13,14).…”

Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination

“…Fifty cytokines, chemokines, and other soluble mediators were assessed by xMAP multiplex assays (Panomics/Affymetrix, Santa Clara, CA), as previously described (22). Multiplex soluble-mediator data were analyzed on the BioPlex 200 array system (Bio-Rad Technologies, Hercules, CA) with a lower boundary of 100 beads per analyte per sample.…”