Abstract
BackgroundCalprotectin (S100A8/A9 or MRP8/14) and S100A12 (leukocyte-derived proteins), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) are markers of inflammation and angiogenesis. Ultrasound (US) is sensitive for detection of greyscale synovitis and power Doppler (PD) vascularization. The objective of the present study was to explore the associations between calprotectin, S100A12, IL-6, VEGF, erythrocyte sedimentation rate, C-reactive protein and a comprehensive US assessment in patients with rheumatoid arthritis (RA) starting biologic disease-modifying anti-rheumatic drug (bDMARD) treatment.MethodsA total of 141 patients with RA were assessed by US, clinical examination and biomarker levels at baseline and at 1, 2, 3, 6 and 12 months after initiation of bDMARDs. US assessment of 36 joints and 4 tendon sheaths were scored semi-quantitatively (0–3 scale). European League Against Rheumatism (EULAR) response was calculated. Statistical assessments performed to explore the associations between biomarkers and US sum scores included Spearman’s rank correlation analysis as well as linear and linear mixed model regression analyses.ResultsCalprotectin showed the overall strongest correlations with both US sum scores (rs = 0.25–0.62) and swollen joint counts (of 32) (rs = 0.24–0.47) (p < 0.05 at all examinations). An association with US sum scores remained after we adjusted for age, sex, disease duration and all the other markers in a regression analysis at baseline. Decreased calprotectin at the first month was predictive of both EULAR response (p ≤ 0.001) and decreased sum PD scores at 3, 6 and 12 months (p ≤ 0.05).ConclusionsCalprotectin had the highest association with US synovitis and predicted treatment response. It may thus be considered as a marker for evaluating inflammation and responsiveness in patients with RA on bDMARD treatment.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) identifier: ACTRN12610000284066. Registered on 8 April 2010 (retrospectively registered).
Highlights
Calprotectin (S100A8/A9 or MRP8/14) and S100A12, interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) are markers of inflammation and angiogenesis
Baseline levels of calprotectin, S100A12 and IL-6 were significantly higher in patients than in control subjects, but this was not shown for VEGF (Table 1)
IL-6 was significantly elevated after baseline in sera of patients starting with tocilizumab (n = 12, 8.5%) (Additional file 1: Figure S1)
Summary
Calprotectin (S100A8/A9 or MRP8/14) and S100A12 (leukocyte-derived proteins), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) are markers of inflammation and angiogenesis. Calprotectin and S100A12 can be chemoattractants for neutrophils and monocytes/ mast cells, respectively [7] and can in several ways contribute to recruitment of leukocytes to inflammatory sites. Both proteins have, when measured in plasma or serum, been repeatedly reported to be associated with clinical disease activity in RA [8,9,10,11,12,13,14,15,16,17,18]. Calprotectin was associated with radiographic damage in a cross-sectional study and predicted radiographic progression in a longitudinal study [11, 19], whereas S100A12 has shown a weak association with radiographic damage in a small longitudinal study [17]
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