Myeloid-related Protein 8/14 Levels in Rheumatoid Arthritis: Marker of Disease Activity and Response to Methotrexate

2016 ◽  
Vol 43 (4) ◽  
pp. 731-737 ◽  
Author(s):  
Pradeepta Sekhar Patro ◽  
Ankita Singh ◽  
Ramnath Misra ◽  
Amita Aggarwal

Objective.Myeloid-related proteins (MRP) 8/14 belong to a family of calcium-binding proteins produced by myeloid cells. Baseline serum levels of MRP8/14 have been shown to predict response to biologicals in rheumatoid arthritis (RA). Because methotrexate (MTX) is the first-line therapy in RA, we studied whether MRP8/14 levels can predict response to MTX.Methods.Patients with active RA disease who were naive to disease-modifying antirheumatic drugs were enrolled. All patients were treated with MTX only, to a maximum of 25 mg/week or the maximal tolerated dose. At 4 months, the European League Against Rheumatism response was assessed. All patients who needed rescue therapy after 2 months or who did not respond at 4 months were classified as nonresponders.Results.Ninety patients were enrolled, of whom 3 discontinued MTX within 4–6 weeks, so 87 patients were analyzed [74 women, median (interquartile range; IQR) for the Disease Activity Score at 28 joints (DAS28) was 4.43 (4.1–5.1)]. The median (IQR) serum MRP8/14 level at baseline was 19.95 µg/ml (11.49–39.06). The serum MRP8/14 had good correlation with DAS28-C-reactive protein (CRP; r = 0.35, p = 0.001). The MRP8/14 levels fell significantly after 4 months of treatment (10.28 µg/ml, 5.95–16.05, p < 0.001). Among 87 patients, 69 were responders. The median (IQR) baseline level of MRP8/14 was higher among responders compared with nonresponders: 23.99 µg/ml (15.39–42.75) versus 9.58 µg/ml (6.11–24.93, p = 0.00250). The levels declined in the responders, from 23.99 µg/ml (15.39–42.75) to 10.41 µg/ml (5.83–15.61, p < 0.001), but not in the nonresponders, from 9.58 µg/ml (6.11–24.93) to 9.19 µg/ml (7.74–21.96, p = 0.687). Receiver-operation characteristic analysis showed that MRP8/14 was a better predictor of response than CRP and erythrocyte sedimentation rate, especially with early disease onset (< 1-yr duration).Conclusion.MRP8/14 is a good marker of disease activity in RA, and higher levels predict response to MTX.

2019 ◽  
Vol 59 (1) ◽  
Author(s):  
Katie Tuckwell ◽  
Cem Gabay ◽  
Thierry Sornasse ◽  
Ruediger Paul Laubender ◽  
Jianmei Wang ◽  
...  

Abstract Background Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA. Objectives To evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). Methods Baseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined. Results Overall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response. Conclusions Although CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.


2014 ◽  
pp. 475-481 ◽  
Author(s):  
O. SGLUNDA ◽  
H. F. MANN ◽  
H. HULEJOVÁ ◽  
O. PECHA ◽  
L. PLEŠTILOVÁ ◽  
...  

Interleukin-21 (IL-21) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The aim of our study was to assess serum levels of IL-21 in patients with recent-onset RA in relation to disease activity and response to treatment. We analyzed serum levels of IL-21 in 51 RA patients, both before and 12 weeks after the initiation of treatment and in 36 healthy individuals. Disease activity was assessed at baseline and at weeks 12 and 24 using the Disease Activity Score for 28 joints, serum levels of C-reactive protein, and the total swollen joint count. We found that IL-21 levels were not increased in patients with recent-onset RA compared with healthy controls, but they had significantly decreased from baseline to week 12 during treatment. Baseline levels of IL-21 significantly correlated with measures of disease activity (p<0.02 for all). Although IL-21 levels did not predict achievement of remission, decrease in IL-21 levels correlated with improvement in disease activity after 12 weeks (p<0.02) and also after 24 weeks (p<0.04) of treatment. Our data suggest that circulating IL-21 levels may serve as a biomarker of disease activity and better outcome in early phase of RA.


2019 ◽  
Vol 57 (3) ◽  
pp. 274-279 ◽  
Author(s):  
A. S. Avdeeva ◽  
A. M. Satybaldyev ◽  
N. V. Demidova ◽  
N. Yu. Nikishina ◽  
E. V. Gerasimova ◽  
...  

Objective:to analyze therapy with rituximab (RTM) in real clinical practice according to the data available in OREL registry of patients with active rheumatoid arthritis (RA).Subjects and methods. The analysis included 349 patients. All the patients received RTM: 340 – the original drug (MabThera®) and 9 – the biosimilar Acellbia®. 263 patients (75.4%) received RTM in combination with disease-modifying anti-rheumatic drugs (DMARDs) and 86 (24.6%) – RTM as monotherapy.Results and discussion. Of the 349 patients included in the analysis, 272 (77.9%) patients received RTM as the first biologic agent (BA) (263 patients were treated with the original drug and 9 – with the biosimilar) and 77 (22.1%) patients had previously used the BA. The majority of patients (n=205 (58.7%)) received three or more; 109 (31.2%) patients – one, and 35 (10%) – two RTM courses of RTM therapy. RTM caused a significant reduction in disease activity just after the first therapy course and in the levels of acute-phase reactants (C-reactive protein (CRP) and ESR); after the fifth therapy course, median CRP concentration decreased by 1.4 times and amounted to 7 [1.2; 17.9] mg/l and that of ESR reduced by 1.8 times and was 10 [5; 20] mm/hr (p<0.05).Conclusion.The analysis of RTM therapy in RA patients in real clinical practice demonstrated that in most cases RTM was given as the first BA, in combination with DMARDs, the main agent of which was methotrexate. The use of RTM was accompanied by a significant reduction in disease activity and in the serum levels of acute-phase reactants and autoantibodies.


2012 ◽  
Vol 39 (4) ◽  
pp. 694-700 ◽  
Author(s):  
KAZUKO SHIOZAWA ◽  
YOSHIKO KAWASAKI ◽  
TAKASHI YAMANE ◽  
RYOSUKE YOSHIHARA ◽  
YASUSHI TANAKA ◽  
...  

Objective.To study the contribution of anticitrullinated protein antibody (ACPA), and especially of its titer, to radiographic progression and disease activity in rheumatoid arthritis (RA).Methods.Patients with RA (n = 396) who attended a Japanese clinic within 2 years after disease onset were divided into the following groups according to second-generation (ACPA-2) ACPA titer on their first visit: negative (0–4.4 U/ml; n = 115), low-positive (4.5–121 U/ml; n = 141), and high-positive (> 121 U/ml; n = 140). The ACPA-2-positive groups were further subdivided into lowest (4.5–32 U/ml), low (33–121 U/ml), high (122–277 U/ml), and highest (> 278 U/ml) quartiles. All patients were treated with disease-modifying antirheumatic drugs (DMARD) including methotrexate, but not biologics. Subsequent radiographic progression and disease activity for 2 years were prospectively evaluated using the van der Heijde-modified Sharp score (SHS) and 28-joint Disease Activity Score (DAS28).Results.After treatment with DMARD, the disease activity (including number of swollen joints, number of tender joints, duration of morning stiffness, DAS28-erythrocyte sedimentation rate, and DAS28-C-reactive protein) was significantly decreased in all patient groups. Disease activity and radiographic progression as revealed by the change in SHS remained relatively higher in the ACPA-2 low- and high-positive groups as compared with the ACPA-2-negative group. The relationship between the titer of ACPA-2 at baseline and subsequent radiographic progression was not exactly linear, and the extent of disease activity or radiographic progression was similar between ACPA-2 low- and high-positive groups and also between ACPA-2 lowest- and highest-positive quartile groups. The results were demonstrable in cumulative SHS probability plots, and also repeatable in seronegative patients, which indicated that the titer of ACPA-2 is not a predictor of disease activity or radiographic progression in RA, and ACPA-2-negative patients, especially those with < 3 U/ml, showed minimal radiographic progression.Conclusion.Presence of ACPA-2, but not its titer, at baseline is a predictor of radiographic progression or disease activity, where radiographic progression is minimal in ACPA-2-negative patients.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1101.2-1101
Author(s):  
H. Hajji ◽  
K. Maatallah ◽  
H. Ferjani ◽  
W. Triki ◽  
D. Ben Nessib ◽  
...  

Background:Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that affects both small and large joints. Hip involvement is an evolutionary turning point in RA and significantly alters the patient’s quality of life.Objectives:This study aimed to assess characteristics of RA patients with hip involvement.Methods:It was a cross-sectional study, including patients with RA (according to 2010 ACR/European League Against Rheumatism (EULAR) criteria).We divided patients into two groups: G0 patients without hip involvement, G1 patients with hip involvement. Hip involvement was defined with a limited movement during examination with abnormalities on standard radiographs. We collected the following data: age, the disease activity score (DAS28), the inflammatory biomarkers C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR), Rheumatoid Factor (RF), and Anti Citrullinated Peptides Antibodies (ACPA), and SHARP score (A scoring system used to assess the radiological changes in patients with RA. It describes erosions and narrowing of the joint space of 27 small joints of the hands, including the carpal bones and feet).Results:Among the 224 patients included, 25had hip involvement (11%). The male / female sex-ratio was higher in G1 (0.66 vs 0.22, p=0.017).Patients in G1 were younger at disease onset (44,16±16,11 years vs 51.9±13.9 years, p= 0.022) and had a longer disease duration (12,28 ± 11,49 years vs 6,2010 ± 6,45 years, p=0.02). They had also higher HAQ(1,7692 vs 1,3054, p=0.05).SHARP score was higher in G1 (176.32 vs. 106.88, p=0.011). Atlantoaxial subluxation was more common in G1 (32% vs 14%,p=0.035).When comparing the groups we did not find any significant difference regarding age (56.12 ± 11.88 years vs 58,24±12,26 years, p=0.341), disease activity (DAS28-ESR:5.41 vs. 5.65, p=0.380; DAS28-CRP: 5.19 vs. 5.51, p=0.290), ESR (53.88 vs. 46.95, p=0.237), CRP:23,8894 vs 22,89, p=0.975), and in the serological profile (RF; G1:68% vs G0: 70.8%, p=0.817, ACPA; G1: 60% vs G0:69%, p=0.366).Conclusion:Patients with hip involvement were commonly male, were younger at disease onset and had more functional impairment based on the HAQ score. C1-C2 dislocation wasalso more common in this group.The SHARP score was also significantly higher in G1, which shows a severe and destructive disease.Disclosure of Interests:None declared


2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Mohamed Taha ◽  
Olfat Gamil Shaker ◽  
Enas Abdelsalam ◽  
Noha Taha

Abstract Background Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. MicroRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data. Methods One hundred and twenty Egyptian patients with RA and 130 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC = 0.85, whereas serum APRIL superiorly distinguished the two groups with AUC = 1 (sensitivity and specificity = 100% at cutoff> 4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. In RA group, serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction. Conclusion Our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
You-Jung Ha ◽  
Dong Woo Han ◽  
Ji Hyoun Kim ◽  
Sang Wan Chung ◽  
Eun Ha Kang ◽  
...  

Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p<0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p=0.001) and IL-6 (p<0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p=0.007) and TNF-α (p=0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p=0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p=0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.


2020 ◽  
Author(s):  
Mohamed Taha ◽  
Olfat Gamil Shaker ◽  
Enas Taha ◽  
Noha Taha

Abstract Background: Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. microRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data. Methods: 120 Egyptian patients with RA and 30 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results: Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC=0.83, whereas serum APRIL superiorly distinguished the two groups with AUC=1 (sensitivity and specificity= 100% at cutoff>4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. Serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction. Conclusion: our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 is a predictor of RA risk and APRIL is an excellent biomarker for disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.


2020 ◽  
Author(s):  
Mohamed Taha ◽  
Olfat Gamil Shaker ◽  
Enas Taha ◽  
Noha Taha

Abstract Background: Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. microRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data.Methods: 120 Egyptian patients with RA and 130 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results: Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC=0.85, whereas serum APRIL superiorly distinguished the two groups with AUC=1 (sensitivity and specificity= 100% at cutoff>4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. In RA group, serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction.Conclusion: our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.


2009 ◽  
Vol 36 (10) ◽  
pp. 2190-2194 ◽  
Author(s):  
MUHAMMAD S. SOYFOO ◽  
JOHANNES ROTH ◽  
THOMAS VOGL ◽  
ROLAND POCHET ◽  
GUY DECAUX

Objective:S100A8 and S100A9 are calcium binding proteins of the S100 family highly expressed in neutrophils and monocytes. S100 proteins are novel ligands of TLR4 important in modulating inflammation. High levels of S100A8/A9 found in human inflammatory diseases are a marker of disease activity in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). We determined levels of S100A8/A9 in sera of patients with systemic lupus erythematosus (SLE) and analyzed their relation to clinical variables of disease activity.Methods.A group of 93 patients with SLE were studied over a period of 3 years, and 143 serum samples were analyzed. S100A8/A9 serum concentrations were determined by a sandwich ELISA. Sera from 10 primary Sjögren’s syndrome (pSS) patients and 50 healthy volunteers were used as controls. Correlations to SLEDAI, ANA, anti-dsDNA, WBC, CH50, C4, and CRP were made. In addition, infections were recorded in all SLE patients.Results.Serum levels of S100A8/A9 were significantly (p = 0.04) higher in SLE patients (1412 ± 664 ng/ml) versus healthy controls (339 ± 35 ng/ml) and pSS patients (400 ± 85 ng/ml). The only significant correlation (r = 0.219; p = 0.015) was found was between S100A8/A9 and SLEDAI. Further, SLE patients with concomitant infections had higher serum levels of S100A8/A9 (39300 ± 13375 ng/ml) than those without infections (1150 ± 422 ng/ml).Conclusion.Serum levels of S100A8/A9 are significantly raised in SLE versus pSS patients and healthy controls and can be correlated to a disease activity index. S100A8/A9 is a more relevant marker of infection in SLE patients.


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