scholarly journals Pre-analytical and analytical confounders of serum calprotectin as a biomarker in rheumatoid arthritis

2019 ◽  
Vol 58 (1) ◽  
pp. 40-49
Author(s):  
Lieve Van Hoovels ◽  
Bert Vander Cruyssen ◽  
Laura Bogaert ◽  
Stefanie Van den Bremt ◽  
Xavier Bossuyt

Abstract Background There is a need for additional biomarkers to assist in the diagnosis and prognosis of rheumatoid arthritis (RA). The aim of our study was to evaluate the (pre-analytical, analytical and clinical) performance of serum calprotectin as a marker of inflammation in RA. Methods The study population included 463 rheumatologic patients (including 111 RA patients and 352 controls) who for the first time consulted a rheumatologist, 20 healthy controls and 27 patients with an infectious disease. Calprotectin was measured (using four different assays) in serum or in serum and EDTA plasma (healthy controls and infectious disease group). For rheumatologic patients, results for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were available. Results Results for blood calprotectin were assay- and matrix-dependent, with higher values found in serum than in plasma. Serum calprotectin was higher in RA patients than in rheumatologic diseased controls and in healthy controls. Serum calprotectin was lower in RA patients than in patients with an infectious disease. Serum calprotectin was associated with disease activity (DAS score). The area under the curve (AUC) to discriminate RA from controls was 0.756 for CRP, 0.714 for ESR and 0.726–0.783 for calprotectin. Conclusions Our data document that calprotectin measurement is assay- and matrix-dependent. Serum calprotectin is associated with disease activity. Additional (prospective) studies are warranted to further evaluate the prognostic and diagnostic value of blood calprotectin measurements.

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Eman A. Baraka ◽  
Mona G. Balata ◽  
Shereen H. Ahmed ◽  
Afaf F. Khamis ◽  
Enas A. Elattar

Abstract Background This study aimed to measure the serum and synovial interleukin (IL)-37 levels in rheumatoid arthritis (RA) patients compared to patients with primary knee osteoarthritis (PKOA) and healthy controls and to detect its relation to RA disease activity. Results This cross-sectional study included 50 RA patients with a mean age of 40.24 ± 8.62 years, 50 patients with PKOA with a mean age of 56.69 ± 4.21, and 40 healthy controls with a mean age of 41.75 ± 7.38 years. The mean serum IL-37 level in the RA patients (382.6 ± 73.97 pg/ml) was statistically significantly (P < 0.001) the highest among the studied groups; however, it showed a non-significant difference between the PKOA patients (70.38 ± 27.49 pg/ml) and the healthy controls (69.97 ± 25.12 pg/ml) (P > 0.94). Both serum and synovial IL-37 levels were significantly positively correlated with disease activity scores (r = 0.92, P< 0.001 and r = 0.85, P < 0.001), tender joint counts (r = 0.83, P < 0.001 and r = 0.82, P < 0.001 ), swollen joint counts (r = 0.72, P < 0.001 and r = 0.60, P < 0.001), visual analog scale (r = 0.82, P < 0.001 and r = 0.82, P < 0.001), erythrocyte sedimentation rate (r = 0.75, P < 0.001 and r = 0.65, P < 0.001), and C-reactive protein (r = 0.93, P < 0.001 and r = 0.79, P < 0.001), respectively. Conclusion Serum and synovial IL-37 were significantly elevated in the RA patients, and they were closely correlated. Being less invasive, the serum IL-37 could be a marker of disease activity and could reflect the effective disease control by drugs. Having an anti-inflammatory effect could not suggest IL-37 as the key player to control inflammation alone, but its combination with other anti-proinflammatory cytokines could be investigated.


2010 ◽  
Vol 37 (4) ◽  
pp. 704-710 ◽  
Author(s):  
KIORI SHIO ◽  
HIROKO KOBAYASHI ◽  
TOMOYUKI ASANO ◽  
RIE SAITO ◽  
HARUYO IWADATE ◽  
...  

Objective.To measure concentrations of the thrombin-cleaved isoform of osteopontin (OPN) in urine and plasma of patients with rheumatoid arthritis (RA), and to assess whether levels of thrombin-cleaved OPN are associated with measures of RA.Methods.Subjects comprised 70 patients with RA, 20 patients with osteoarthritis (OA), and 46 healthy controls. RA disease activity was evaluated by tender joint count, swollen joint count, patient’s global assessment of disease activity, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF), as well as 28-joint count Disease Activity Score (DAS28). OPN levels in plasma and urine were measured by ELISA.Results.Median levels of thrombin-cleaved OPN in urine (U-half) were significantly higher in RA patients (143.5 pmol/mmol Cr) than in healthy controls (67.9 pmol/mmol Cr) or OA patients (69.8 pmol/mmol Cr). Thrombin-cleaved OPN was not detected in plasma. U-half levels correlated significantly with levels of CRP (r = 0.26, p = 0.03), ESR (r = 0.26, p = 0.03), and RF (r = 0.28, p = 0.03). Median U-half levels were significantly higher in patients with stage III (249.9 pmol/mmol Cr) and IV (251.6 pmol/mmol Cr) disease than in patients with stage I (98.6 pmol/mmol Cr) disease.Conclusion.Our results suggest that urine levels of the thrombin-cleaved isoform of OPN may reflect the severity of active inflammatory arthritis in patients with RA.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Ting Xia ◽  
Xing-feng Zheng ◽  
Bao-hua Qian ◽  
He Fang ◽  
Jun-jie Wang ◽  
...  

Interleukin- (IL-) 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA) and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP), were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1βwere analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28) and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA.


2017 ◽  
Vol 31 ◽  
pp. 039463201774935 ◽  
Author(s):  
Monica Gioia Marazzi ◽  
Filippo Randelli ◽  
Marco Brioschi ◽  
Lorenzo Drago ◽  
Carlo Luca Romanò ◽  
...  

There is still no “gold standard” for the diagnosis and prognosis of post-operative periprosthetic joint infection (PJI). Among serum biomarkers, an emerging molecule is presepsin, the soluble fraction of CD14, recently described in other settings as a powerful diagnostic tool to detect sepsis at different degrees of severity. The aim of this study was to investigate the diagnostic and prognostic value of presepsin in PJI. A total of 30 patients with PJI and 30 patients without PJI were enrolled. Presepsin, C-reactive protein (CRP), serum interleukin (IL)-6, triggering receptor expressed on myeloid cells 1 (TREM-1), CCL2, matrix metalloproteinase 9 (MMP-9), CD163, osteopontin (OPN), and toll-like receptor 2 (TLR2) were measured at different times after surgery. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Presepsin showed greater diagnostic value than CRP and IL-6; CD163, TREM-1, and MMP-9 had very low diagnostic potential. Presepsin, OPN, CCL2, suPAR, and TLR2 all decreased significantly with increasing time of recovery after surgery in PJI patients. Presepsin can be considered a useful tool for the diagnosis and clinical monitoring of PJI and can be backed by a panel of new inflammatory markers involved in monocyte-/macrophage-mediated inflammatory responses, such as OPN, CCL2, TLR2, and suPAR.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Lucie Andrés Cerezo ◽  
Markéta Kuklová ◽  
Hana Hulejová ◽  
Zdeňka Vernerová ◽  
Nikola Kaspříková ◽  
...  

Objective. Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA.Methods.PGRN levels were evaluated in patients with RA (n=47) and OA (n=42) and healthy controls (n=41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP), disease activity score (DAS28-CRP), and health assessment questionnaire (HAQ) was studied.Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1±100.2and221.5±102.5versus128.1±34.7 ng/mL;P<0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5±275.3versus241.4±165.2 ng/mL;P=0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r=0.327,P=0.049) and HAQ score (r=0.323,P=0.032), while synovial fluid PGRN correlated only with HAQ (r=0.310,P=0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies.Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.


2015 ◽  
Vol 16 (3) ◽  
pp. 207-211 ◽  
Author(s):  
Dragan Vasiljevic ◽  
Aleksandra Tomic-Lucic ◽  
Sandra Zivanovic ◽  
Mirjana Milosavljevic ◽  
Snezana Radovanovic ◽  
...  

Abstract In this study, we investigated the concentration of serum homocysteine (Hcy) in patients with rheumatoid arthritis (RA) compared with the control group and the connection between homocysteine and parameters of inflammation and disease activity. Sixty RA patients and 20 healthy controls were included in the study, and clinical examination and investigation were performed during which disease activity was assessed. Peripheral blood samples were used for all of the assays. Levels of Hcy were 33% higher in the RA patients than in the control subjects (mean +/− SD 11.79±3.72 μmol/L versus 8.90±1.38 μmol/L; p< 0.01). A significant correlation was found between parameters of inflammation (C-reactive protein) and homocysteine in patients (r=0.322, p=0.012). Patients with high disease activity had a significantly greater increase in homocysteine (p<0.05). An increase in plasma homocysteine in RA patients is related to the parameters of inflammation and disease activity. Elevated Hcy levels occur commonly in patients with RA and may explain some of the increased cardiovascular mortality seen in RA patients.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 524.3-525
Author(s):  
M. Patanè ◽  
L. Carmisciano ◽  
E. Hysa ◽  
E. Gotelli ◽  
A. Signori ◽  
...  

Background:Rheumatoid arthritis (RA) is a long-term, progressive, and disabling autoimmune disease1. The disease activity can be quantified by the Disease Activity Score 28-joint count – C reactive protein (DAS28crp)2; the evaluation of disability function (DF) is actually mainly performed only by subjective Patient Reported Outcomes (PROs) like Health Assessment Questionnaire (HAQ)3; to investigate the functional aspects of RA hands it is usually used the grip strength (GS)4. However, in the scientific literature no tool, which objectively evaluates movement speed, has been reported. The Hand Test System (HTS, ETT) is an engineered glove (RAGLOVE), nowadays applied for neuroscience studies to evaluate hand motility5Objectives:To objectively evaluate the RA hand’s speed of the fine movements, through the HTS and to compared with a group of age and sex matched healthy controls. To verify the correspondence with the HAQ, DAS28, GS.Methods:55 consecutives RA patients (pts) (6 males, age 61 ± 16 years, mean duration of disease 12 ± 8 years), classified according to 2010 ACR/EULAR criteria6, and 50 matched healthy controls (HCs) were enrolled. After consent, all participants undergone HTS test that recognizes the touches between the finger tips during the opposition movements of the hands in standard sequences of movements, after dressed the glove. A multiple finger evaluation (MFE) and a single finger evaluation (SFE) were performed using a dedicated software that provided the physician the following quantitative parameters: Touch Duration (TD), Inter Tapping Interval (ITI) and Movement Rate (MR). Average time for hand 2 minutes. RA pts compiled the HAQ, performed the GS and a DAS28cpr was performed.The student’s t-test was used to compare the glove’s parameters between the groups whereas the analysis of variance (ANOVA) was utilized to verify potential differences between the populations. In order to evaluate the single correlations, the r and p values of Pearson were employed.Results:For MFE, glove parameters TD and ITI were significantly higher in RA pts than HCs, whereas; MR was significantly lower in RA pts compared to HCs (all p <0.001).For SFE non-affected fingers (not swollen and not tender) of RA pts performed better than a clinically affected fingers, but in any case significantly worse than average HCs fingers (p < 0.001).There is a statistically significant correlation between the GS and MR (r= 0.39 p=0.003) and TD (r=-0.33 p=0.015).TD, ITI e MR of RA pts showed a significant correlation with the total score of the HAQ (r = 0.56, r = 0.39, r = -0.56, all p < 0.001;). DAS28, considered as a continuous variable, proved to be significantly correlated with the TD (r = 0.36, p = 0.009). When the RA patients were grouped according to the disease activity by DAS28cpr7, there was an increase of one third of the TD’s logarithm for each increase in the activity class (linear regression with ordinal predictors, beta = 0.33; 95%CI 0.03, 0.63,p < 0.0297). Finally, even RA pts in remission showed a TD significantly higher compared with HCs (p= 0.034).Conclusion:The RAGLOVE is shown as a new safe and fast tool to evaluate a new objective parameter in the hand’s functionality: the speed of finger movements. In RA pts, an inversely proportional correlation emerges between the speed of movement and disease activity.The significant correlation found with HAQ, highlights the loss of motility of the hands as one of the main determinant of disability. The RAGLOVE is now tested in RA patients undergoing treatment.References:[1]Hakkinen et al Ann Rheum Dis. 2005;[2]Van Der Heijde et al J of Rheum. 1993;[3]Fries et al Arthritis Rheum. 1980;[4]Mathiowetz et al J Hand Surg Am. 1984;[5]Carmisciano et al Eur J Neurol. 2020;[6]Aletaha et al. Ann Rheum Dis. 2010;[7]Aletaha et al Arthritis Rheum 2005.Disclosure of Interests:None declared


Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 829
Author(s):  
Yana Kogan ◽  
Edmond Sabo ◽  
Majed Odeh

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.


2010 ◽  
Vol 37 (12) ◽  
pp. 2452-2461 ◽  
Author(s):  
LIE DAI ◽  
LANG-JING ZHU ◽  
DONG-HUI ZHENG ◽  
YING-QIAN MO ◽  
XIU-NING WEI ◽  
...  

Objective.To determine serum glucose-6-phosphate isomerase (GPI) concentrations in patients with rheumatoid arthritis (RA), and to test whether they correlate with objective measures of disease activity.Methods.Sera from 116 patients with RA, 69 patients with non-RA rheumatic diseases, and 101 healthy controls were analyzed. Levels of soluble serum GPI were measured by ELISA. Histological disease activity was determined with the synovitis score in synovial needle biopsies from 58 of the 116 patients with RA. Thirty-one of the 58 synovium samples were stained for CD68, CD3, CD20, CD38, CD79a, and CD34 by immunohistochemistry. Demographic data were collected, as well as serological and clinical variables that indicate RA disease activity, for Spearman correlation analysis.Results.Serum GPI level correlated positively with the synovitis score (r = 0.278, p = 0.034). Significantly higher soluble GPI levels were detected in the RA sera compared with sera from healthy controls and the non-RA disease controls (2.25 ± 2.82 vs 0.03 ± 0.05 and 0.19 ± 0.57 μg/ml, respectively; p < 0.0001). The rate of serum GPI positivity was significantly higher in the RA patients than in the non-RA disease controls (64.7% vs 10.1%; p < 0.0001). Spearman analysis showed no significant correlation between serum GPI level and Disease Activity Score in 28 joints at baseline. After initiation of antirheumatic treatments, GPI levels decreased significantly (2.81 ± 3.12 vs 1.44 ± 2.09 μg/ml; p = 0.016), paralleling improvement of the disease activity indices.Conclusion.Elevated serum GPI may be involved in the synovitis of RA and may prove useful as a serum marker for disease activity of RA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 985.1-985
Author(s):  
K. Triantafyllias ◽  
S. Liverakos ◽  
C. Noack ◽  
A. Schwarting

Background:Valid assessment of disease activity leads to improvement of long-term outcomes in patients with inflammatory arthritis (1). Optical spectral transmission (OST) is a modern diagnostic tool able to assess the blood-specific absorption of light transmitted through a tissue, promising quantification of inflammation in the finger and wrist joints of patients with rheumatoid arthritis (RA) (commercial device: HandScan – Demcon/Hemics, The Netherlands) (2). Even though an increasing number of studies have evaluated diagnostic value of this new technology in RA patients (2,3), no data exist regarding psoriatic arthritis (PsA).Objectives:To examine for the first time the diagnostic value of OST in detecting inflammation in patients with PsA and to evaluate its relationship with disease activity markers and various epidemiological and anthropometric patient characteristics.Methods:OST-Measurements were performed in a group of PsA patients and a group of healthy controls. The difference between OST in the two groups was statistically examined and relationships of OST with clinical (tender / swollen joint counts, disease activity on a visual analogue scale) and serological disease activity markers were evaluated. Moreover, joint ultrasound (US) examinations were performed in a subgroup of PsA patients and OST associations with a Power Doppler- and a Grey Scale-US score were examined. Finally, relationships of OST with various anthropometric and epidemiologic parameters (BMI, hand-size, gender, age) were assessed.Results:We recruited 49 PsA patients [65.3% female; mean age 53.3 years (± 11.8 SD)] and 114 control subjects [77.2% female; mean age 46 years (± 12.8 SD)]. OST was statistically significantly higher in the patient group, compared to the control group [14.95 (12.04 - 17.18, IQR) vs. 10.31 (7.84 – 13.79, IQR); p<0.001]. OST correlated moderately-strongly with both examined US scores (Power Doppler-score: r = 0.5; p = 0.026 and Grey Scale-score: r = 0.52; p = 0.028). Moreover, OST showed a moderate, statistically significant association with C-reactive protein (CRP) (r = 0,298; p = 0,037). Finally, males had significantly higher OST values than females and OST associated moderately-weakly with body mass index (BMI) in the control group (rho = 0.24; p< 0.001).Conclusion:This is the first report of a possible diagnostic value of OST in patients with PsA. OST correlated with ultrasound and serological activity markers and may thus prove to be a useful tool of disease activity assessment, next to well established diagnostic modalities, such as the joint US. Correlations of OST with patient characteristics implicate the need to take also anthropometric and epidemiological patient characteristics into account when interprenting OST results in order to avoid confounding.References:[1]Katchamart W, et al. Systematic monitoring of disease activity using an outcome measure improves outcomes in rheumatoid arthritis. J Rheumatol 2010;37:1411–1415.[2]Triantafyllias, et al. Diagnostic value of optical spectral transmission in rheumatoid arthritis: associations with clinical characteristics and comparison with joint ultrasonography. J Rheumatol 2020 1;47(9):1314-1322.[3]Onna M Van, et al. Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique. Ann Rheum Dis 2016;75:511–518.Disclosure of Interests:Konstantinos Triantafyllias Speakers bureau: Pfizer, Novartis, Janssen, Chugai, Stefanie Liverakos: None declared, Claudia Noack: None declared, Andreas Schwarting: None declared


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