scholarly journals Will 14-3-3η Be a New Diagnostic and Prognostic Biomarker in Rheumatoid Arthritis? A Prospective Study of Its Utility in Early Diagnosis and Response to Treatment

2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Doaa Shawky Alashkar ◽  
Radwa Mostafa Elkhouly ◽  
Amira Yousef Abd Elnaby ◽  
Doaa Waseem Nada

Aim of the Work. To evaluate diagnostic and prognostic capacity of 14-3-3η protein in early RA, investigate its pathogenic and theragnostic role, and find its correlations with disease activity and severity in established RA patients. Subjects and Methods: 80 patients with early RA, 80 patients with established RA, and 80 healthy controls were included in this study. ROC curve analysis of RF, ACCP, and 14-3-3η in early disease was conducted, and serum levels of 14-3-3η were assessed by ELISA and reassessed in early RA patients 6 months after anti-TNF therapy. Correlation of 14-3-3η with parameters of disease activity and severity was analyzed. Results. Serum14-3-3η levels were significantly higher in all RA patients than in controls P < 0.001 , its sensitivity was 86.7% and 88.3% in early and established RA patients with a significant difference with RF and ACCP at early disease, and the specificity was 96.7%. There was a significant reduction of 14-3-3η levels 6 months after treatment in the first group p = 0.004 , and there was a significant positive correlation between serum 14-3-3η levels and parameters of disease activity and severity. Conclusion. 14-3-3η could be a novel, potent, and efficacious diagnostic, and prognostic marker for RA with high sensitivity, that may become a new therapeutic target for RA.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1848.2-1849
Author(s):  
M. A. Mortada ◽  
H. Eitta ◽  
R. Elmallah ◽  
A. Radwan ◽  
A. Elsaman

Background:Musculoskeletal Ultrasonography (MSUS) is now a widely used tool for monitoring of rheumatoid arthritis (RA). Although there are many proposed sets of composite scores, a fixed set of joints may not be an ideal tool to assess a disease like RA, which affects many joints and tendons in different presentations. In previous study (1) U9 score was proven to be correlated with disease activity parameters.Objectives:To determine whether US assessment using U9 score is useful for monitoring response to treatment for RA or not?Methods:A prospective, multicenter study were conducted in period from July 2019 to December 2019. All recruited RA patients were subjected to: Disease activity assessment by clinical disease activity indices (CDAI and DAS28 ESR). Functional status assessment by (HAQ) and ultrasonographic assessment using U9 score which include 8 joints (bilateral wrists,2ndMCP,3RDMCP and knees) plus most clinically affected joint or tendon (one joint or one tendon). Most clinically affected joints from 48 joints. Any affected tendons could be choosing. All targeted joints were evaluated according to EULAR guidlines and by EULAR/ OMERACT combined score (0-3). Targeted tendons were scored (0-3).All patients received their treatment (biologic and non biologic DMARDs) according to the decision of the treating physicians. No specific therapy is needed. CDAI and DAS28 ESR, HAQ and U9 score were repeated after 3 months to detect the response to change after receiving the therapy.Results:One hundred and forty patients (23.6% were male) with mean age 39.26±11.30 were recruited from 4 tertiary referral university hospitals.There was a significant difference (<0.001) between the first and second visits as regards clinical, laboratory and ultrasonographic parameters. DAS 28 decreased form (5.29±1.21) to (3.95±0.99), ESR decreased from (42.12±15.24) to (26.84±12.32), HAQ2 improved from (0.652±0.350) to (0.510±0.237) and U9 total US score decreased from (13.56±5.18) to (8.02±4.28).There was significant correlation between U9 ultrasonographic score and clinical parameters at both visits (table 1).Table 1.correlation between U9 ultrasonographic score and clinical parameters.U9 at 1stvisitU9 at 2ndvisitDAS-28Pearson Correlation(P value)0.806<0.0010.790<0.001CDAIPearson Correlation(P value)0.787<0.0010.773<0.001HAQPearson Correlation(P value)0.431<0.0010.317<0.001We found that the most suitable cut-off value of U9 score to predict high disease activity was 11.5 (sensitivity 85.7% and specificity 80.6%), cut off value for moderate disease activity was 5.5(sensitivity 83.2% and specificity 88%) and cut off value for low disease activity was 3.5 (sensitivity of 83.3% and specificity 57.1%). These results are summarized in the following table:Conclusion:U9 ultrasonographic score is very useful method for evaluating the monitoring the response of treatment.References:[1]Mortada, et al. Annals of the Rheumatic Diseases 2019;78:1009.Disclosure of Interests:None declared


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.


2020 ◽  
Author(s):  
jingxian Wang ◽  
Peiyan Zheng ◽  
Zhifeng Huang ◽  
Huimin Huang ◽  
Mingshan Xue ◽  
...  

Abstract Background: Some patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. Methods: Sixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n=9), an improvement group (n=13), and a stable group (n=14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed. Results: Compared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = -0.323, p = 0.018; KL-6: rS = -0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001). Conclusions: Serum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.


2021 ◽  
Vol 13 (3) ◽  
Author(s):  
Shokrollah Salmanzadeh ◽  
Razieh Mombeini ◽  
Seyed Mohammad Alavi ◽  
Morteza Abdullatif Khafaie

Background: Tuberculosis (TB) is a major health problem worldwide. To date, the standard diagnostic method for TB is still the direct observation of Mycobacterium TB in a sputum smear or culture. Objectives: There is an urgent need for a method to detect the disease in a shorter time with acceptable sensitivity and specificity and help monitor the treatment. Methods: A panel of 34 adults newly diagnosed with smear-positive pulmonary TB was followed during their treatment period of five months. Neopterin (NPT) serum levels were measured three times (before treatment and two and five months after treatment) using the Brahms ELItest Neopterin kit, and the results were analyzed using descriptive and graphical methods. Results: The mean NPT for the first time before treatment was 27.47 ± 20.7 nmol/L. NPT was measured two months after the anti-TB treatment, and the associated mean was 16.97 ± 14.14 nmol/L. At the end of the fifth month, the mean NPT concentration reached 11.3 ± 10.5 nmol/L. The mean serum NPT before treatment had a statistically significant difference with the mean NPT at the end of the second and fifth months of the treatment (P = 0.001). Conclusions: According to the national protocol for treating TB, a sputum smear is still necessary for patients’ follow-up. It seems that the serum NPT level should be measured to monitor response to treatment in patients that, for any reason are not able to give sputum in TB treatment follow-up.


2019 ◽  
Author(s):  
Qingwen Jiang ◽  
Xu Zheng ◽  
Yiting Li ◽  
Weina Huang ◽  
Xinjian Li ◽  
...  

Abstract Background: Lung cancer has become the leading cause of cancer-related death in China. However, most of patients were diagnosed at advanced stage. Thus, novel lung cancer diagnostic tests, which can be used to screen individuals in early stage, are required.Methods: A total of 208 patients involving 161 cases of lung cancer and 47 cases of benign diseases were enrolled. Serum concentration of GTM, CETM, PTM, CTM, ETM and HTM were analyzed by kits according to the manufacturer’s guidelines.Results: The results showed significant difference in serum concentrations of GTM, CETM, PTM, CTM, ETM, and HTM between patients with lung cancer and benign diseases. In addition, when compared with benign diseases, higher levels of those six markers were also observed in patient with SCC and SCLC, but not for ADC. Receiver operating characteristic (ROC) curves were further suggested a high sensitivity and specificity of six markers to identify lung cancer.Conclusion: The serum levels of GTM, CETM, PTM, CTM, ETM and HTM in lung cancer were significantly higher than those of benign diseases. Moreover, these six biomarkers showed a high sensitivity and specificity to identify a patient with malignant. These findings suggested that detection of those six biomarkers in serum might be helpful for differential diagnosis of lung cancer.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingxian Wang ◽  
Peiyan Zheng ◽  
Zhifeng Huang ◽  
Huimin Huang ◽  
Mingshan Xue ◽  
...  

Abstract Background Some patients with interstitial pneumonia with autoimmune features (IPAF) showed a progressive course despite therapy. This study aimed to evaluate whether serial changes in the serum levels of surfactant protein-A (SP-A) and Krebs von den Lungen-6 (KL-6) can predict disease progression. Methods Sixty-four patients with IPAF and 41 patients with non-fibrotic lung disease (non-FLD) were examined. Based on long-term changes in lung function, 36 IPAF patients who were followed up for more than 3 months were divided into a progressive group (n = 9), an improvement group (n = 13), and a stable group (n = 14). Serum KL-6 and SP-A levels were measured. The sensitivity, specificity, cut-off value, and area under the curve (AUC) value for each of the indices were determined using receiver operating characteristic (ROC) curve analysis. The expression differences in these biomarkers and their correlation with disease severity were analyzed. Results Compared with non-FLD patients, serum SP-A and KL-6 levels in IPAF patients were increased significantly [SP-A: (p < 0.001); KL-6: (p < 0.001)] and negatively correlated with DLCO (SP-A: rS = − 0.323, p = 0.018; KL-6: rS = − 0.348, p = 0.0011). In patients with progressive disease, the posttreatment serum SP-A and KL-6 levels were increased significantly compared with pretreatment levels [SP-A: (p = 0.021); KL-6: (p = 0.008)]. In patients showing improvement, the levels were decreased significantly [SP-A (p = 0.007) and KL-6 (p = 0.002)]. Changes in serum biomarkers (Delta SP-A and Delta KL-6) were significantly negatively correlated with changes in lung function (Delta FVC, Delta DLCO and Delta FEV1) (rS = 0.482, p < 0.05). A significant positive correlation was found between Delta SP-A and Delta KL-6 (rS = 0.482, p < 0.001). Conclusions Serum SP-A and KL-6 offer high sensitivity and specificity for the diagnosis of IPAF. The decrease in serum SP-A and/or KL-6 levels in patients with IPAF is related to the improvement in pulmonary function. SP-A and KL-6 may be important biomarkers for predicting disease progression in patients with IPAF.


2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Sahar A. Elsayed ◽  
Omar M M. Mohafez

Abstract Background Specific autoantibodies are considered as an important marker in autoimmune rheumatic diseases and are of great value for the diagnosis and prognosis of systemic lupus erythematosus (SLE) patients. A total of eighteen autoantibodies were analyzed for their positivity in SLE patients and we evaluated the clinical relevance of the five most frequent autoantibodies: anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro60, and anti-Ro52 on disease activity and renal affection in SLE Egyptian patients. Results Immunological profile and correlation of the five autoantibodies with disease activity and histopathological pattern of renal involvement were analyzed for 190 SLE patients. Lupus nephritis (LN) patients showed much worse constitutional and mucocutaneous manifestations than patients without nephritis. Autoantibody profile showed a significant increased frequency of anti-dsDNA, anti-nucleosome, anti-histone, anti-Ro-60, and anti-Ro52 antibodies in LN patients. The impact of the co-positivity of the autoantibodies on the renal function was obvious. Moreover, the disease activity increased by the increased frequency of autoantibodies positivity in LN patients. ROC curve analysis showed that anti-nucleosome had the highest sensitivity; 93% followed by anti-dsDNA 83.3% then anti-histone 73.8%, but anti-Ro60 and anti-Ro52 showed a humble sensitivity. Furthermore, the highest frequency of positivity for the five autoantibodies was found in class-III and class-IV LN patients. Conclusion Detection of anti-dsDNA, anti-nucleosome, anti-histone, and anti-Ro60 in SLE patients may be important for predicting disease progression and kidney affection. Moreover, anti-nucleosome and anti-dsDNA show high sensitivity and specificity for lupus nephritis, thus patients with four to five positive autoantibody panels should be kept under close monitoring as they may warrant considering aggressive therapy to control their disease and prevent renal damage.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1442.2-1443
Author(s):  
E. Aleksandrova ◽  
A. Novikov ◽  
E. Luchikhina ◽  
D. Karateev ◽  
G. Lukina

Background:YKL-40 (chitinase-3-like 1 protein, human cartilage glycoprotein 39) is one of the major proteins secreted locally in the arthritic joint by activated macrophages, chondrocytes, synoviocytes and neutrophils, YKL-40 an important marker for inflammation, cartilage remodelling and synovial hyperplasia is recognized as a possible auto-antigen in rheumatoid arthritis (RA).Objectives:The aims of the study were to determine the serum level of YKL-40 in early RA and investigate his relationship with biomarkers of disease activity and joint destruction.Methods:We studied 22 patients with early RA (ACR/EULAR 2010 classification criteria); 4 males, 18 females; median and interquartile range (25th—75th percentile) of age 55,0 (43,0-64,0) years, disease duration 7,0 (5,0-11,0) months, DAS28 4,9 (4,3-5,8); 86% IgM rheumatoid factor (IgM RF) +; 91% anti-cyclic citrullinated peptide antibody (anti-CCP) +. All patients were treated with methotrexate (MTX). Three (14 %) patients received low oral doses of steroids and intra-articular injections. The control group included 22 healthy donors (HC). Radiographs were scored according to the van der Heijde-modified Sharp score. YKL-40, matrix metalloproteinase-3 (MMP-3), anti-CCP were detected using commercially available enzyme-linked immunosorbent assays (ELISA). The serum levels of IgM RF, C-reactive protein (CRP), serum amyloid A (SAA) were measured by immunonephelometry.Results:RA patients had significantly higher serum level of YKL-40 than HC (92,1; 68,5-153,1 pg/ml vs 54,0; 41,7-83,2 pg/ml, p<0.01). Serum YKL-40 concentration was positively correlated with DAS 28 (r=0,5; p<0,05), erythrocyte sedimentation rate (ESR) (r=0,5; p<0,05), CRP (r=0,8; p<0,05), SAA (r=0,6; p<0,05) and MMP-3 (r = 0,6; p<0,05). We found no relationship between the level of YKL-40 and articular radiographic changes.Conclusion:Elevated serum concentration of YKL-40 in early RA is associated with clinical and laboratory indicators of disease inflammatory activity and increased level of MMP-3 - an immunological marker of joint destruction.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Elena Luchikhina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Consultant of: Abbvie, Biocad, Sanofi, Celgene, Dmitriy Karateev Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Lilly, Bayer, Paid instructor for: Abbvie, Pfizer, Biocad, Sanofi, Novartis, Lilly, Galina Lukina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Paid instructor for: Abbvie, Biocad, Sanofi, Celgene


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 632.2-632
Author(s):  
S. Piantoni ◽  
S. Masneri ◽  
F. Regola ◽  
C. Nalli ◽  
A. Tincani ◽  
...  

Background:Soluble intercellular adhesion molecule 1 (ICAM1) and C-X-C motif chemokine 13 (CXCL13) were described as differentially associated with two major subtypes of synovitis in rheumatoid arthritis (RA). Raised serum levels of ICAM1 (which is upregulated in synovial fibroblasts in response to TNFα), and of CXCL13 (which is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells), are associated with a myeloid or lymphoid synovial phenotype, respectively (1). It has been suggested that a preferential clinical response to anti-TNFα, as compared to anti-IL-6R monotherapy, can be predicted by measuring these two biomarkers (2). No information is available on the possible utility of these biomarkers in RA patients treated with abatacept (ABA), a T-cell co-stimulation blocker.Objectives:To analyze the effect of ABA on ICAM1 and CXCL13 serum levels in RA and to verify whether they predict the response to the drug.Methods:63 RA patients [F/M=51/12; median (10th-90thpercentile) age=60 (41-72) years; CRP-DAS28=4.6 (3.3-5.8); ACPA positive: 86%], before and after 6 months of treatment with ABA + methotrexate and 22 sex and age-matched healthy controls (HC) were evaluated. Serum ICAM1 and CXCL13 levels were dosed by commercial ELISA (Life Technologies and R&D). Response to treatment was defined with the EULAR criteria.Results:CXCL13 serum levels were higher in RA at baseline than in HC [136 (42-325) vs 32 (19-57) pg/ml, p<0.01], while no difference was observed in ICAM1 [186 (125-276) vs 184 (153-246) ng/ml, p=0.9]; positive correlations between ICAM1 and CRP (r:0.28; p=0.03) and CXCL13 levels and CRP (r:0.40; p<0.01) and CRP-DAS28 values (r:0.27, p=0.05) were found. After therapy with ABA, a reduction of CXCL13 was observed [136 (42-325) vs 94 (29-319) pg/ml, p<0.01], both in responders [n: 37: 151 (57-462) vs 97 (26-329) pg/ml; p<0.01] and non-responders (n: 14: 142 (68-293) vs 89 (42-198) pg/ml; p=0.01]. Not significant variation of ICAM1 serum levels was found in the entire cohort [186 (125-276) vs 190 (113-252) ng/ml, p=0.06]. However, a significant decrease was observed in non-responders [222 (169-302) vs 186 (110-233) ng/ml, p=0.02]. At baseline, no significant difference was found among patients seropositive for ACPA if compared with the negative ones [ACPA+ vs ACPA- for ICAM1 [187 (123-280) vs 177 (134-258) ng/ml; p=0.7] and for CXCL13 [143 (42-368) vs 113 (56-270) pg/ml; p=0.4]].Conclusion:Our results confirmed that CXCL13 serum levels are directly correlated with disease activity and demonstrated that ABA therapy induces their reduction. These findings suggest that the co-stimulation blockade at central level and/or in the synovium lead to a reduced production of CXCL13. We could not demonstrate that CXCL13 levels predict the clinical response to ABA in this cohort of patients.References:[1]Rosengren S, Rheumatology 2011;2.Dennis G, Arthritis Res Ther 2014Acknowledgments:Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduction.Disclosure of Interests:None declared


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