There were wide variations in expectations among patients. Multiple demographic, psychological, and clinical characteristics were associated with expectations, with disability due to pain being the most consistently associated variable.
Objective
Rho-kinases (ROCKs) have been implicated in the pathogenesis of cardiovascular and renal disorders. We recently showed that ROCKs could regulate the differentiation of murine TH17 cells and production of IL-17 and IL-21, two cytokines associated with SLE. The goal of this study was to assess ROCK activation in human TH17 cells and evaluate ROCK activity in SLE patients.
Methods
An ELISA-based ROCK activity assay was employed to evaluate ROCK activity in human cord blood CD4+ T cells differentiated under TH0 or TH17 conditions. We then performed a cross-sectional analysis of 28 SLE patients and 25 healthy matched controls. ROCK activity in peripheral blood mononuclear cell (PBMC) lysates was assessed by ELISA. Cytokine and chemokine profiles were analyzed via ELISA.
Results
Human cord blood CD4+ T cells differentiated under TH17 conditions expressed higher levels of ROCK activity than CD4+ T cells stimulated under TH0 conditions. Production of IL-17 and IL-21 was furthermore inhibited by addition of a ROCK inhibitor. SLE PBMCs expressed significantly higher levels of ROCK activity as compared to healthy controls, 1.25 vs. 0.56, respectively (p=0.0015). Sixteen (57%) SLE patients expressed high ROCK levels (OD450>1). Disease duration, lymphocyte count, and azathioprine use were significant independent predictors of ROCK activity in multivariable analyses.
Conclusions
Consistent with previous results in the murine system, increased ROCK activation was associated with TH17 differentiation. Enhanced ROCK activity was furthermore observed in a subgroup of SLE patients. These data support the concept that the ROCK pathway could represent an important therapeutic target for SLE.
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