The soluble biomarker calprotectin (a S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab

Abstract

IntroductionCalprotectin (MRP8/MRP14, S100A8/A9) is associated with disease activity in patients with rheumatoid arthritis (RA). Ultrasonography (US) is a reliable method for evaluation of synovitis (B-mode (BM) and power Doppler (PD)). The present objectives were to explore in RA patients the associations between calprotectin and a comprehensive US examination, as well as the responsiveness of calprotectin compared to other inflammatory markers during anti-TNF treatment.MethodsA total of 20 RA patients starting treatment with adalimumab were examined longitudinally by US (BM and PD (semi-quantitative scores 0 to 3) of 78 joints, 36 tendons/tendon groups and 2 bursae) and clinically at baseline and after 1, 3, 6 and 12 months. Associations between the US sum scores and the inflammatory markers calprotectin, serum amyloid A (SAA), CRP and ESR were explored by correlation and linear regression analyses, and the response to treatment was assessed by Standardized Response Mean (SRM).ResultsThe inflammatory markers, clinical examinations and US sum scores improved during treatment (P < 0.001). Of the inflammatory markers, calprotectin had the highest correlation coefficients with the total BM and PD sum scores (median (range) 0.59 (0.37 to 0.76) for BM and 0.56 (0.38 to 0.72) for PD). Even higher correlations were found between calprotectin and sum US scores of reduced number of joint counts. Calprotectin made a considerable contribution to total US sum scores in the linear regression analyses (P = 0.001 to 0.031) and among the inflammatory markers, calprotectin had the highest SRM (0.84 at one month).ConclusionsCalprotectin was associated with the sum scores from a comprehensive US assessment and was responsive to change during anti-TNF treatment. Thus, examination of this leukocyte protein could be of additional value in the assessment of RA patients on biologic treatment.

Serum Calprotectin Versus Acute‐Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

“…Higher calprotectin levels have been found in synovial fluid and serum from RA and PsA patients compared with healthy controls and osteoarthritis patients (11). Calprotectin serum levels correlate with disease activity, predict relapse, and are independently associated with radiographic progression in RA (12)(13)(14). Calprotectin serum levels decrease significantly after TNFi treatment (15), and therefore monitoring of the response to biologic therapy might be useful (16).…”

Calprotectin in rheumatic diseases

“…72 A recent study by Inciarte-Mundo et al 84 showed that CLP was associated with synovitis at the ultrasonography assessment in RA and psoriatic arthritis (PSA) patients in remission. CLP serum levels had the highest discriminatory capacity compared to CRP and ESR and a cut-off of 1.66 mg/ml for synovitis presence was also identified.…”

“…67 CLP serum levels correlate with disease activity and are associated with markers of more severe RA in many studies. 48,49,61,64,66,[68][69][70][71][72][73][74][75][76] CLP has been found to be higher in the serum of rheumatoid factor 48,49,69,70,71,73 and anticitrullinated peptide positive patients 23,49,64,72 compared with seronegative ones. 23 CLP correlates with inflammatory indices, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and serum amyloid A protein (SAA) and inversely with TNF-a inhibitors through levels.…”

“…48,[74][75][76][77][78] CLP serum levels can decrease in response to treatment with both conventional and biologic disease modifying anti-rheumatic drugs. 72,[74][75][76][77][78][79][80] Indeed, CLP serum levels have shown a prompt and more marked response to inflammatory changes compared with classic inflammatory indices, thus representing a sensitive biomarker for assessing treatment response. 72,74 This finding is supported by evidence of S100A8 and S100A9 expression in PMNs decreasing after treatment with TNF-a inhibitors.…”

“…72,[74][75][76][77][78][79][80] Indeed, CLP serum levels have shown a prompt and more marked response to inflammatory changes compared with classic inflammatory indices, thus representing a sensitive biomarker for assessing treatment response. 72,74 This finding is supported by evidence of S100A8 and S100A9 expression in PMNs decreasing after treatment with TNF-a inhibitors. 79 Baseline CLP serum levels were higher in responders to treatment compared with non-responders and their decrease was predictive of treatment response in some studies, 74,75,80 but not in all.…”