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

Abstract

Objective. To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels. Methods. We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]). Results. Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ‡1 swollen joint (1.74 mg/ml versus 3.04 mg/ml; P 5 0.010). Using DAS28 ‡2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ‡2.47 mg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (r 5 20.671, P < 0.001) and IFX (r 5 20.729, P 5 0.017). Conclusion. Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acutephase reactants, even in patients with low inflammatory activity.

Calprotectin as a Biomarker for Melioidosis Disease Progression and Management

“…CALP is a potent activator of innate immunity mediated through Toll-like receptor 4 (9) and is primarily a product of neutrophils. Elevated serum CALP levels are associated with inflammatory diseases (10,11), while fecal CALP assays are widely used to differentiate inflammatory bowel disease from irritable bowel syndrome and ulcerative colitis (12). In the present study, we confirm that serum CALP levels are elevated in NHPs with respiratory infections caused by B. pseudomallei and examine the possibility of using CALP as a general biomarker for clinical responses during the acute and eradication phases of antibiotic treatment in human cases of melioidosis.…”

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

“…In addition, calprotectin and S100A12 can be chemoattractants for neutrophils and monocytes/mast cells, respectively [7] and can thus 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 [8–18]. In addition, 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].…”

Calprotectin in rheumatic diseases: a review

“…Inciarte-Mundo et al [17] in a cross-sectional study included 87 patients with rheumatoid arthritis, receiving adalimumab, etanercept or infliximab for at last 3 months. They demonstrated that calprotectin stratified disease activity in rheumatoid arthritis patients receiving TNF-α inhibitors more accurately than the acute-phase reactants such as CRP and erythrocyte sedimentation rate (ESR), whichever composite index was assessed (the Disease Activity Score in 28 joints [DAS28], the Clinical Diseases Activity Index [CDAI] or the Simplified Disease Activity Index [SDAI]).…”

“…Only calprotectin level distinguished between RA patients in clinical remission and those with low disease activity according to all indices analyzed. MRP8/14 serum level correlated inversely with TNF-α inhibitors trough serum levels [17]. In another study, Inciarte-Mundo et al [18] analyzed associations between calprotectin, ESR, CRP and disease activity indices in 33 RA patients receiving tocilizumab.…”