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Arthritis Research & Therapy | 2015

Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis.

J. Hurnakova; Jakub Zavada; P. Hanova; Hana Hulejová; Martin Klein; Herman Mann; O. Sleglova; M. Olejarova; Šárka Forejtová; O. Ruzickova; Martin Komarc; Jiri Vencovsky; Karel Pavelka; Ladislav Šenolt

IntroductionCalprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross-sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA.MethodsA total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0–3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis.ResultsThe levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R2 = 0.765, p < 0.001) than CRP (R2 = 0.496, p < 0.001).ConclusionsThe serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients.


PLOS ONE | 2016

Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission

J. Hurnakova; Hana Hulejová; Jakub Zavada; Martin Komarc; P. Hanova; Martin Klein; Herman Mann; O. Sleglova; M. Olejarova; Šárka Forejtová; O. Ruzickova; Jiri Vencovsky; Karel Pavelka; Ladislav Šenolt

Objective Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. Methods Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0–1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. Results The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58–67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity. Conclusion The present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.


PLOS ONE | 2017

Relationship between serum calprotectin (S100A8/9) and clinical, laboratory and ultrasound parameters of disease activity in rheumatoid arthritis: A large cohort study

J. Hurnakova; Hana Hulejová; Jakub Zavada; P. Hanova; Martin Komarc; Herman Mann; Martin Klein; O. Sleglova; M. Olejarova; Šárka Forejtová; O. Ruzickova; Jiri Vencovsky; Karel Pavelka; Ladislav Šenolt

Background Calprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity. Objectives In the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA. Methods A total of 160 patients with RA underwent clinical (swollen joint count—SJC, tender joint count—TJC, Disease Activity Score—DAS28, Clinical Disease Activity Index—CDAI, and simplified Disease Activity Index—SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores. Results Serum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p<0.001), DAS28-CRP (r = 0.346, p<0.001), SDAI (r = 0.305, p<0.001), CDAI (r = 0.279, p<0.001) scores and CRP levels (r = 0.556, p<0.001). Moreover, calprotectin was significantly correlated with GS (r = 0.379, p<0.001) and PD synovitis scores (r = 0.419, p<0.001). The multivariate regression analysis showed that calprotectin is a better predictor of the CDAI score and PD US synovitis than CRP. Conclusions The results of this study support an additional role of calprotectin in assessing inflammatory activity in patients with RA.


Rheumatology | 2018

Entheseal involvement in patients with systemic lupus erythematosus: an ultrasound study

Andrea Di Matteo; Emilio Filippucci; Edoardo Cipolletta; Iulia Satulu; J. Hurnakova; Valentina Lato; Rossella De Angelis; Rudolf Horvath; Karel Pavelka; Fausto Salaffi; Walter Grassi

Objectives The main objective of this study is to explore the prevalence and distribution of entheseal US changes in a cohort of SLE patients, taking as controls a group including both PsA patients and healthy subjects. The secondary objective is to investigate the correlation between the US findings and the clinical and serological data in SLE patients. Methods Clinical and US assessment of quadriceps, patellar and Achilles tendons, and plantar fascia entheses were performed by independent rheumatologists on 65 patients with SLE, 50 patients with PsA and 50 healthy subjects. US findings were identified according to the OMERACT definitions. In SLE patients, the correlation between the US changes and the clinical and laboratory findings was evaluated. Results US revealed one or more abnormalities in at least one enthesis in 44 out of 65 SLE patients (67.7%), 47 out of 50 PsA patients (94.0%) and 22 out of 50 healthy subjects (44.0%). In SLE patients, US findings indicating active inflammation were significantly more frequently detected than in healthy subjects (P < 0.001). The distal enthesis of the patellar tendon was the most commonly involved. The presence of power Doppler signal at the enthesis was an independent predictor of SLE disease activity (SLEDAI-2k P < 0.001, β = 0.52; musculoskeletal-BILAG P < 0.001, β = 0.56). Conclusion The burden of entheseal sonographic changes was significantly higher in SLE patients than in healthy subjects, especially as regards active inflammation. The presence of power Doppler signal at the enthesis may represent a potential biomarker of SLE disease activity.


Annals of the Rheumatic Diseases | 2018

AB0239 Development of a novel „molecular disease activity“ tool composed of 8 serum biomarkers for monitoring rheumatoid arthritis

J. Hurnakova; Martin Komarc; R. Horvath; Hana Hulejová; Jakub Zavada; L. Palova Jelinkova; K. Danova; P. Hanova; H. Mann; Jiri Vencovsky; Karel Pavelka; R. Spisek; Ladislav Šenolt

Background Accurate disease activity measurement is a key component of rheumatoid arthritis (RA) management. In 2012, multi-biomarker disease activity (MBDA) test using 12 serum proteins was presented1. Objectives To develop a novel test for measuring inflammatory activity in RA. Methods Serum samples were obtained from 82 patients with RA (60 females, median disease duration 4.2 years, median age 55.2 years, RF positivity 60.3%, ACPA positivity 69.7%). A detailed stepwise analysis of 20 candidate biomarkers selected from the literature search (IL1β, IL-6, IL-7, IL-8, IL-12p70, IL-17A, IL-22, IL-33, IL-34, IFNγ, VEGF, YKL-40, CXCL-13, MMP-3, resistin, visfatin, leptin, adiponectin, calprotectin and CRP) was performed. Methods of factor analysis (a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors) were used in order to develop a tool composed of different serum markers that would optimally reflect disease activity in RA. Spearman correlation index was used to explore associations between newly designed tool and clinical as well ultrasound parameters (German US7 score) of disease activity. Results We have developed a “Molecular Disease Activity” test covering underlying pathophysiological processes composed of 8 serum markers: calprotectin, CRP, IL-6, MMP-3, VEGF, resistin, IL-22 and IL-7 that optimally reflected inflammatory activity in RA. This model was significantly associated with clinical (DAS28-ESR, DAS29-CRP, CDAI, SDAI) and ultrasound variables (PD syn score, GS syn score) of disease activity in RA, as shown in table 1.Abstract AB0239 – Table 1 Cross-sectional correlations between “Molecular Disease Activity” tool composed of 8 biomarkers and clinical and ultrasound parameters of disease activity Parameters Molecular disease activity(factor score) p (significance) DAS28-ESR 0.664** <0.001 DAS28-CRP 0.666** <0.001 SDAI 0.731** <0.001 CDAI 0.669** <0.001 SJC 0.546** <0.001 GS syn score 0.657** <0.001 PD syn score 0.701** <0.001 ** Correlation is significant at≤0.01 CDAI, Clinical Disease Activity Index; DAS28-CRP, Disease Activity Score with C-reactive protein; DAS28-ESR, Disease Activity Score with erythrocyte sedimentation rate; GS syn, Grey Scale synovitis; PD syn, Power Doppler synovitis; SDAI, Simplified Disease Activity Index; SJC, swollen joint count Conclusions We believe that this newly designed test based on 8 serum markers may contribute to more accurate measurement of inflammatory activity in RA and improvement of patients‘ outcomes. Further evaluation of this tool in a larger cohort is needed. Reference [1] Centola M, Cavet G, Shen Y, et al. Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis. Plos One2013Apr 9;8(4). Acknowledgements Supported by the project of Ministry of Health, Czech Rep. No. 0 23 728 and SVV No. 260 373. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2016

FRI0532 Association between The 7-Joint Ultrasound Score (US7S) and Physical Function in Rheumatoid Arthritis

Jakub Zavada; P. Hanova; J. Hurnakova; Michal Uher; L. Puczokova; Šárka Forejtová; Martin Klein; H. Mann; M. Olejarova; O. Sleglova; Karel Pavelka

Objectives To investigate the longitudinal relationship between physical disability and US7S in a prospective cohort of patients with RA. Methods A cohort of 205 RA pts (49 incident/156 prevalent) (mean±SD age 55±14 years, 47% RF+, 63% ACPA+, DAS28-CRP 3.7±1.5, mHAQ 0.43±0.52, disease duration in incident vs. prevalent pts. 0.9±0.7 vs. 8.1± 8.3 resp.) was followed up longitudinally for 29±9 months. Assessments at baseline and at month 3 and 6, and then every 6 months comprised DAS28-CRP, functional evaluations using the modified Health Assessment Questionnaire (mHAQ) and an ultrasound assessment of the clinically dominant hand and foot by US7S1. US7S consists of 5 subscores for synovitis (syn) and tenosynovitis (ten) assessed by grey-scale (GS) and Power-Doppler (PD), and an erosions score (ES). A linear mixed model was used to assess the longitudinal relationship between US7 subscores and mHAQ. Univariate analyses with an interaction term for incident vs. prevalent disease, and a multivariate analysis (with age, sex, BMI, RF and ACPA status, and DAS28-CRP entered as covariates) were performed. Results In univariate analyses (table) mHAQ was longitudinally associated with GSsyn, PDsyn, PDten and GSten US7 subscores (with resp. β coefficients significantly higher in incident patients), while erosions score was a significant predictor of mHAQ only in prevalent pts. In a multivariate model the US7 subscores were individually no longer significant predictors of mHAQ, although the R2 of the model was improved by addition of US7 items from 43.6 to 46.9 (p<0.001 for improvement of R2).Table 1. Univariate analyses and interaction with incident (i)/prevalent (p) RA (predicted variable – mHAQ) Predictor RA β (95% CI) p-value* p-value** % variability explained – R2 DAS28-CRP all 0.112 (0.100; 0.123) <0.001 0.510 44.5 i 0.120 (0.093; 0.146) <0.001 p 0.110 (0.097; 0.123) <0.001 GSsynUS all 0.008 (0.004; 0.011) <0.001 0.038 3.2 i 0.014 (0.007; 0.021) <0.001 p 0.006 (0.002; 0.010) 0.002 PDsynUS all 0.012 (0.008; 0.016) <0.001 0.018 4.3 i 0.021 (0.012; 0.029) <0.001 p 0.009 (0.004; 0.014) <0.001 GStenUS all 0.018 (0.002; 0.035) 0.032 0.078 1.7 i 0.045 (0.011; 0.080) 0.010 p 0.010 (0.000; 0.020) 0.316 PDtenUS all 0.024 (0.012; 0.037) <0.001 0.032 2.0 i 0.053 (0.024; 0.083) <0.001 p 0.017 (0.010; 0.024) 0.013 ES all 0.009 (−0.003; 0.021) 0.145 0.062 0.3 i −0.021 (−0.055; 0.013) 0.216 p 0.013 (0.001; 0.026) 0.047 *p-value of significance of given β. **p-value of significance of difference between incident and prevalent RA. Conclusions This study provides evidence that RA related activity and damage reflected by US7S contribute to impaired physical function in RA, and their impact differs in early and established disease. When combined with conventional clinical parameters, the additional explanatory value of US7 for mHAQ was only minor. References Backhaus M. et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009 Sep 15;61(9):1194–201 Acknowledgement This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, and IGA grant NT12437 Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2016

SAT0547 Ultrasound Assessment of Cartilage Damage at Metacarpal Head Level in Rheumatoid Arthritis and Osteoarthritis

J. Hurnakova; A Di Matteo; Fausto Salaffi; Marina Carotti; Edoardo Cipolletta; Antonella Draghessi; E. Di Donato; M. Di Carlo; Valentina Lato; Karel Pavelka; Emilio Filippucci; Walter Grassi

Background Ultrasound (US) with very high frequency probe (up to 22 MHz) has a resolution power of 0.1 mm and allows for the direct visualization of the hyaline cartilage of the metacarpal head. Objectives To determine the prevalence and distribution of US-detected cartilage damage at metacarpal heads of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate if cartilage damage evaluated by US method is associated with radiographic scores (Sharp van der Heijde score and Simple Erosion Narrowing Score (SENS) in RA and Kallman score in OA). Methods 50 patients with RA and 19 patients with OA were enrolled in this study. The US examination of the metacarpal head cartilage from II to V finger of both hands was performed. 400 metacarpophalangeal (MCP) joints in RA and 152 MCP joints in OA were scanned with a very high-frequency linear probe (i.e. 10–22 MHz), using a previously described scoring system for cartilage damage1. In a subgroup of 27 patients with RA and 7 with OA the radiographic scores were calculated. Pearsons correlation coefficient and Cohen κ were used to investigate associations between US and radiographic scores. Results The US examination of the metacarpal head cartilage from II to V finger of both hands lasted a mean of 6 minutes. The metacarpal head cartilage was found positive for cartilage damage by US in 139 out of 400 (34.8%) MCP joints in RA and in 65 out of 152 (42.8%) MCP joints in OA. In RA, the hyaline cartilage of the II right metacarpal head was the most frequently affected followed by the II left and the III right metacarpal head. The less affected was the V metacarpal head bilaterally. In OA, cartilage damage was homogeneously distributed in all MCP joints. Symmetric damage of cartilage was observed in 97/400 (24.3%) RA joints and in 44/152 (28.9%) OA joints. Conversely, asymmetric damage of the cartilage was observed in 42/400 (10.5%) RA joints (only in patients with disease duration more than 2 years) and in 21/152 (13.8%) joints in OA. A significant positive correlation was found between US total score and either Sharp van der Heijde score or SENS score (r=0.584, p<0.001; r=0.510, p<0.001, respectively) in RA and between US total score and Kallman score (r=0.687, p<0.001) in OA. Agreement between two imaging methods was high, 78% in RA (κ=0.570, p<0.001) and in 91% in OA (κ=0.750, p<0.001). Conclusions The present study provides evidence supporting the feasibility of the US assessment of the metacarpal head cartilage. A positive significant correlation was found between the US findings, obtained with a very high frequency probe by an experienced sonographer and the radiographic scores assigned by an expert radiologist. References Filippucci E et al: Interobserver reliability of ultrasonography in the assessment of cartilage damage in rheumatoid arthritis. Ann Rheum Dis 2010, 69(10), p. 1845–1848. Acknowledgement Supported by EULAR, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2016

SAT0552 Musculoskeletal Ultrasound (MSUS) Showing Entheseal Involvement in Patients with Systemic Lupus Erythematosus (SLE): Something Unexpected

A Di Matteo; Iulia Satulu; M. Di Carlo; Valentina Lato; Antonella Draghessi; E. Di Donato; J. Hurnakova; Emilio Filippucci; Walter Grassi

Background Musculoskeletal involvement is one of the most common manifestations of SLE and, recently, different studies have demonstrated the role of MSUS in the evaluation of tendons and joints involvement in SLE patients (1). The enthesis is traditionally not included as a potential target of the inflammatory process of the disease, remaining a yet unexplored anatomical area in this cohort of patients. Objectives To investigate the prevalence and distribution of entheseal abnormalities in SLE patients using MSUS. Methods 30 consecutive SLE patients were enrolled in the present study. The scanned entheses were those included in the Glasgow Ultrasound Enthesitis Scoring System: the patellar insertion of the quadriceps tendon (QT), the patellar and distal insertion of the patellar tendon (PT), the calcaneal insertion of the Achilles tendon (AT) and the calcaneal insertion of the plantar fascia (PF). All patients underwent both clinical and ultrasound examination aimed at assessing the entheseal involvement. MSUS entheseal pathology was evaluated by detecting the presence of grey scale changes and power Doppler (PD) signal, as defined by the OMERACT Ultrasound Task Force (2). All the factors that may affect the MSUS findings at entheseal level (lipid profile, body mass index, history of trauma, sport activity and corticosteroid therapy) were carefully evaluated. Results MSUS entheseal abnormalities were found in 20 out of the 30 patients (66.6%) and in 59 of the 300 entheses examined (19.6%). Patients were clinically asymptomatic in 71.4% of the cases. Among the entheses affected, the distal insertion of the PT was the most commonly involved area (37.2%), followed by the calcaneal insertion of the AT (22%) and the proximal insertion of the PT (16.9%). The patellar insertion of the QT and the calcaneal insertion of the PF were involved in the 13.5% and 10.4% of the cases respectively. With regard to the pathological changes PD signal, hypoechoic areas and entheseal thickening were the most frequently detected abnormalities (29.3%, 26.7% and 24.1%, respectively). Calcifications and bone erosions were found in 11.3% and 8.6% of the cases respectively. Conclusions Although the inflammatory process in SLE patients is traditionally considered to be localized at synovial tissue level, this study shows that entheseal changes are not uncommon in SLE, especially at PT insertions, occurring frequently in asymptomatic patients. These preliminary results should lead to further investigations aimed at identifying the factors associated with entheseal involvement in SLE patients. References Gabba A et al. Joint and tendon involvement in systemic lupus erythematosus: an ultrasound study of hands and wrists in 108 patients. Rheumatology (Oxford). 2012 Dec; 51:2278–85. Terslev L et al. Defining enthesitis in spondyloarthritis by ultrasound: result of a Delphi process and of a reliability reading exercise; Outcome Measures in Rheumatology Ultrasound Task Force. Arthritis Care Res 2014; 66:741–8. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2016

AB0952 Serum Visfatin and Resistin, but Not Adiponectin or Leptin, Are Associated with Ultrasound Synovitis in Patients with Rheumatoid Arthritis

J. Hurnakova; R. Horvath; K. Danova; Jakub Zavada; H. Mann; L. Palova Jelinkova; Hana Hulejová; P. Hanova; Martin Klein; O. Sleglova; Martin Komarc; M. Olejarova; Šárka Forejtová; O. Ruzickova; Radek Spisek; Jiri Vencovsky; Karel Pavelka; Ladislav Šenolt

Background Adipocytokines are soluble mediators secreted by adipose tissue and immune cells with potent immune regulatory functions. Some adipocytokines have been previously associated with disease activity and radiographic progression in patients with rheumatoid arthritis (RA)1. Objectives To investigate associations between adipocytokines, clinical and traditional laboratory markers as well as with ultrasound synovitis in patients with RA. Methods A total of 82 patients with RA (62 females, median disease duration 4.2 years) were enrolled into this study. All patients underwent clinical examination (swollen joint count - SJC, tender joint count – TJC, Disease activity score - DAS28-ESR and DAS28-CRP, Clinical disease activity index - CDAI, Simplified disease activity index - SDAI). Moreover, ultrasound examination of 7 selected joints mostly affected in RA (wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints) was performed to measure synovial hypertrophy in Grey Scale (GS) and pathological neovascularization in Power Doppler (PD) using semi-quantitative grading 0–33. Blood samples were taken at the same day as clinical and ultrasound assessments. Serum concentrations of adiponectin, resistin, visfatin, leptin and CRP were measured. Clinical and laboratory measures were correlated with ultrasound findings using Spearmans correlation coefficient. Results Serum visfatin and resistin levels were associated with the disease activity (Figure 1) and correlated significantly with DAS28-ESR (r=0.473, p<0.001; r=0.363, p<0.001, resp.), DAS28-CRP (r=0.443, p<0.001; r=0.348, p<0.005, resp.), SDAI (r=0.431, p<0.001; r=0.344, p<0.005, resp.), CDAI (r=0.419, p<0.001, r=0.344, p<0.005, resp.) and with CRP levels (r=0.456, p<0.001; r=0.364, p<0.001, resp.). Moreover, visfatin and resistin levels significantly correlated with GS (r=0.430, p<0.001, r=0.273, p<0.05, resp.) and PD synovitis scores (r=0.309, p<0.01, r=0.283, p=0.01, resp.). Neither leptin nor adiponectin correlated with parameters of disease activity in patients with RA. Conclusions Our study supports circulating visfatin and resistin as promising serum pro-inflammatory biomarkers reflecting clinical, laboratory as well as ultrasound parameters of synovial inflammation in RA. References Senolt L, Krystufkova O, Hulejova H, Kuklova M, Filkova M, Cerezo LA, Belacek J, Haluzik M, Forejtova S, Gay S, Pavelka K, Vencovsky J: The level of serum visfatin (PBEF) is associated with total number of B cells in patients with rheumatoid arthritis and decreases following B cell depletion therapy. Cytokine 2011, 55: 116–121 Acknowledgement This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared


Annals of the Rheumatic Diseases | 2015

FRI0592 Serum Calprotectin is Associated with Ultrasound-Determined Active Synovitis in Patients with Rheumatoid Arthritis

J. Hurnakova; Jakub Zavada; Hana Hulejová; P. Hanova; Martin Komarc; Martin Klein; H. Mann; S. Olga; M. Olejarova; Šárka Forejtová; O. Ruzickova; Jiri Vencovsky; Karel Pavelka; Ladislav Šenolt

Background Calprotectin (S100A8/9, MRP8/14) is a promising circulating biomarker reflecting disease activity in patients with rheumatoid arthritis (RA). In two small previous studies in RA patients1,2, serum calprotectin correlated with ultrasound synovial inflammation. Objectives To investigate associations between serum calprotectin, clinical and ultrasound-determined disease activity in a larger cohort of RA patients in a cross-sectional study. Methods A total of 167 patients with RA (134 females) were enrolled in this study. All patients underwent clinical assessment (SJC, TJC, DAS28-ESR) and ultrasound examination according to the US-7 score3 to assess synovitis by gray-scale (GS) and power Doppler (PD) using semiquantitative grading (0-3). Serum calprotecin was measured by ELISA. Associations between serum calprotectin, C-reactive protein (CRP) and clinical as well as ultrasound findings were explored using Spearmans correlation coefficient. A multiple regression analysis was used to determine the predictive value of calprotectin (mg/l), CRP (mg/l) and DAS28 for GS and PD synovitis score. Results Serum calprotectin significantly correlated with DAS28 (r=0.357, p<0.001), SJC (r=0.258, p=0.001), TJC (r=0.181, p<0.05), ESR (r=0.386, p<0.001) and particularly with CRP levels (r=0.540, p<0.001). In addition, calprotectin was also associated with GS (r=0.341, p<0.001) and PD synovitis (r=0.313, p<0.001). Using a multivariate linear regression model with calprotectin, CRP and DAS28-FW as explanatory variables, calprotectin and DAS28, but not CRP, were significant predictors for GS (β=0.371, p<0.001; β=0.598, p<0.001, resp.) and PD synovitis (β=0.346, p<0.001; β=0.379, p<0.001, resp.). Conclusions This study confirms in a large cohort of RA patients that serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of disease activity. Calprotectin is more closely associated with local joint inflammation than CRP and thus may represent a more specific circulating biomarker for monitoring synovial inflammation in RA patients. References Hammer HB, Fagerhol MK, Wien TN, Kvien TK. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther. 2011;13(5):R178. Hurnakova J, Hanova P, Hulejova H, et al. Serum calprotectin (S100A8/9) correlates with clinical and ultrasound outcomes in patients with early rheumatoid arthritis. In Ann Rheum Dis. 2014; Suppl (2):658–658. Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009 Sep 15; 61(9):1194-1201. Acknowledgements This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared

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Karel Pavelka

Charles University in Prague

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Jakub Zavada

Charles University in Prague

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Ladislav Šenolt

Charles University in Prague

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Martin Komarc

Charles University in Prague

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P. Hanova

Charles University in Prague

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M. Olejarova

Charles University in Prague

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Hana Hulejová

Charles University in Prague

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O. Sleglova

Charles University in Prague

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Šárka Forejtová

Charles University in Prague

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Jiri Vencovsky

Charles University in Prague

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