Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis

Hammer, Hilde Berner; Ødegård, Sigrid; Fagerhol, Magne K.; Landewé, Robert; Heijde, Desirée van der; Uhlig, Till; Mowinckel, Petter; Kvien, Tore K

doi:10.1136/ard.2006.064741

Cited by 130 publications

(138 citation statements)

References 36 publications

(25 reference statements)

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…Similar correlations between disease activity and calprotectin have been documented in RA and PsA patients receiving sDMARDs (12,35,36). Only calprotectin serum levels were significantly lower in RA patients in remission than in those with low disease activity, whatever the composite activity index used, a finding also observed in PsA patients.…”

Section: Discussionsupporting

confidence: 75%

“…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).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Inciarte-Mundo

Hernández

Ruíz-Esquide

et al. 2016

Arthritis Care & Research

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

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

Inciarte-Mundo

Hernández

Ruíz-Esquide

et al. 2016

Arthritis Care & Research

View full text Add to dashboard Cite

show abstract

“…Activated macrophages in the pannus tissue produce multiple factors that control both immunity and bone homeostasis, creating an imbalance between bone formation and bone resorption in favor of the latter, resulting in severe bone destruction (2,25). Of the various factors produced in the inflamed synovium, S100A8 and S100A9 are the most upregulated, and they are produced in excessive amounts (4)(5)(6). In the S100A8/A9 heterodimer complex, S100A8 is the active component, and S100A9 stabilizes S100A8 to prevent its degradation (7).…”

Section: Discussionmentioning

confidence: 99%

“…The "alarmins" S100A8 and S100A9, which are key players in the initiation and amplification of inflammatory responses (3), are the most up-regulated proteins present in RA synovial fluid, and they are significantly correlated with arthritis severity and joint degradation (4)(5)(6). S100 proteins are low molecular weight calcium-binding proteins produced mainly by monocytes, macrophages, and neutrophils and are secreted upon activation.…”

mentioning

confidence: 99%

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

Grevers¹,

Vries²,

Vogl³

et al. 2011

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Rheumatoid arthritis, which is associated with elevated levels of S100A8 and S100A9, is characterized by severe bone erosions caused by enhanced osteoclast formation and activity. The aim of the present study was to investigate the role of S100A8 and S100A9 in osteoclastic bone destruction in murine antigen-induced arthritis (AIA).Methods. Bone destruction was analyzed in the arthritic knee joints of S100A9-deficient mice in which S100A8 protein expression was also lacking, and in wild-type (WT) controls. Osteoclast precursors from S100A9-deficient and WT mice were differentiated into osteoclasts in vitro. Additionally, precursors were stimulated with S100A8, S100A9, or S100A8/A9 during osteoclastogenesis. Receptor involvement was investigated using an anti-receptor for advanced glycation end products (anti-RAGE)-blocking antibody, soluble RAGE, or Toll-like receptor 4 (TLR-4)-deficient osteoclast precursors. The formation of osteoclasts and actin rings, the regulation of osteoclast markers, and bone resorption were analyzed.Results. Bone erosions and cathepsin K staining were significantly suppressed in S100A9-deficient mice after AIA induction. However, osteoclast precursors from S100A9-deficient mice developed normally into functional osteoclasts, which excludes a role for intrinsic S100A8/A9. In contrast to the results observed with S100A9 and S100A8/A9, the addition of S100A8 during osteoclastogenesis resulted in stimulation of osteoclast formation in conjunction with enhanced actin ring formation and increased bone resorption. Analysis of the putative receptor for S100A8 in osteoclastogenesis revealed that osteoclast differentiation and function could not be inhibited by blocking RAGE, whereas the increase in osteoclast numbers and enhanced bone resorption were completely abrogated using TLR-4-deficient osteoclast precursors.Conclusion. These results demonstrate that S100A8 stimulated osteoclast formation and activity and suggest that both S100A8 and TLR-4 are important factors in mediating osteoclastic bone destruction in experimental arthritis.Bone erosions are an important hallmark of rheumatoid arthritis (RA) and typically result from enhanced formation and activity of osteoclasts in affected joints. Osteoclasts originate from hematopoietic precursors of the monocyte/macrophage lineage that differentiate into multinucleated osteoclasts under the

show abstract

“…[26] Serum levels of S100A8/S100A9 were found to correlate better with disease activity and joint destruction in various inflammatory arthritides than classical markers of inflammation. [27] Much research has been done to assess the levels of inflammatory marker CRP, ESR, IL-6 etc in chronic periodontitis. Since periodontitis shares common immunomodulatory profile with Rheumatoid Arthritis, the role of alarmins in chronic inflammatory condition like periodontitis need to be evaluated.…”

Section: Alarmins As Biomarkers Of Diagnosis and Prognosismentioning

confidence: 99%

“Adapting to terminologies involved in host immune response”

Raveendran¹

2013

IOSR-JDMS

View full text Add to dashboard Cite

Calprotectin (a major leucocyte protein) is strongly and independently correlated with joint inflammation and damage in rheumatoid arthritis

Abstract: Calprotectin was found to significantly and independently explain the variation in the radiological and clinical assessments of joint damage. Longitudinal studies are required to examine whether calprotectin may predict the progression of joint damage in RA.

Cited by 130 publications

References 36 publications

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

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

S100A8 enhances osteoclastic bone resorption in vitro through activation of Toll‐like receptor 4: Implications for bone destruction in murine antigen‐induced arthritis

“Adapting to terminologies involved in host immune response”

Contact Info

Product

Resources

About