Protein biochip array technology for cytokine profiling predicts etanercept responsiveness in rheumatoid arthritis

Abstract

In rheumatoid arthritis (RA) there are currently no useful indicators to predict a clinical response to tumour necrosis factor-alpha (TNF-alpha) blockade. The purpose of this study was to determine the role of peripheral blood cytokine profiling in differentiating between a good versus poor response to etanercept in RA. Peripheral blood samples were collected at baseline and at 3 months from 33 patients with active disease who were treated twice weekly by etanercept therapy. Responders are defined by the presence of three of four American College of Rheumatology criteria: > or =20% decrease in C-reactive protein (CRP), visual analogue score of disease activity, erythrocyte sedimentation rate and improvement of the disease activity score (28; four values) by > or =1.2 obtained at 3 months. Twelve cytokines were measured from serum collected on days 0 and 90 by proteomic array (protein biochip array, Investigator Evidence, Randox France), including interleukin (IL)-6, TNF-alpha, IL-1a, IL-1b, IL-2, IL-8, interferon-gamma, IL-4, IL-10, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF) and vascular endothelium growth factor. Our results showed that high serum levels of MCP-1 and EGF were associated with a response to etanercept. In addition, the increase of two combined parameters CRP and EGF was predictive of a response to etanercept treatment at 3 months (sensitivity: 87.5% and specificity: 75%, accuracy: 84.4%). These findings suggest that cytokine profiling by proteomic analysis before treatment initiation may help to identify a responder patient to TNF-alpha blocking agents in RA.

Figures

Fig. 1

Cytokine level evolution during etanercept treatment in the responder (R) and non-responder (NR) groups. Box-plots are on the right and representations of the mean (±standard deviation intervals) on the left in each group at each time (MCP1, monocyte chemoattractant protein-1; EGF, epidermal growth factor; IL6, interleukin-6, TNFA, tumour necrosis factor-α).

Fig. 2

Cytokine level evolution during etanercept treatment in the responder and non-responder groups. Box-plots are on the right and representations of the mean (±standard deviation intervals) on the left in each group at each time (CRP, C-reactive protein).