Calprotectin (S100A8/A9) has the strongest association with ultrasound-detected synovitis and predicts response to biologic treatment: results from a longitudinal study of patients with established rheumatoid arthritis

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 (r s = 0.25–0.62) and swollen joint counts (of 32) (r s = 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).Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1201-0) contains supplementary material, which is available to authorized users.

Calprotectin, a new biomarker for diagnosis of acute respiratory infections

“…The response of calprotectin to bacterial respiratory infections is well in line with previous reports demonstrating increase in calprotectin in sepsis [17][18][19][20] as well as other inflammatory conditions with neutrophil activation such as appendicitis, synovitis and prosthetic joint infections [21][22][23] .…”

The role of calprotectin in rheumatoid arthritis

“…GS score is generally used for synovitis evaluation and PD score is for vascularization evaluation in the joints of RA. [52] Studies demonstrated a correlation between CLP levels and US sum scores, GS and PD synovitis scores. [7,52] Additionally, Hurnakova et al [53] analyzed the value of serum CLP levels for PD synovitis in RA by a multivariate regression analysis.…”

“…The noteworthy association between serum CLP and swollen joint count (SJC), tender joint count (TJC) was observed in several studies. [3,7,52,53] CLP circulatory levels have significant correlations with grip strength (r = -0.22, P < 0.05) and circumferences of proximal interphalangeal (PIP) joints (r = 0.33, P < 0.05) in a cross-sectional study of 70 RA patients. [4] Above studies also suggested an association of serum CLP and other serological indicators.…”

“…[4] Above studies also suggested an association of serum CLP and other serological indicators. [7,52,53] A systematic analysis highlighted that CLP was positively correlated with CRP and ESR (r = 0.8, P < 0.01; r = 0.7, P < 0.01) in RA. [2] In addition, serum CLP levels were also associated with rheumatoid factor (RF) levels (r = 0.25, P < 0.05).…”

Utilization of longitudinal ultrasound measurements to quantify changes in knee joint synovial vascularity in a rabbit model of rheumatoid arthritis

“…Vascular endothelial growth factor (VEGF) is an important pro-inflammatory factor that has a role in the pathogenesis of RA, and is also the most important and most powerful known pro-angiogenic factor [11,12]. Rheumatologists have examined the role of VEGF in the angiogenesis of RA, and the effect of inhibition of VEGF as a potential therapy for RA.…”