Serum Uric Acid as a Potential Biomarker in Patients With Rheumatoid Arthritis-associated Interstitial Pneumonia (RA-ILD)

Abstract Background: Uric acid (UA) has been reported participate in various inflammatory and autoimmune diseases. Increasing evidence has shown that UA also plays an important role in lung inflammation and fibrosis. We aimed to investigate the correlation between UA and rheumatoid arthritis (RA), especially rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods: 266 RA patients and 138 healthy individuals were recruited in this study. RA was identified according to ACR/EULAR 2010 criteria. UA in serum and bronchoalveolar lavage fluid (BALF), as well as clinic and laboratory Indexes were collected from participants enrolled in the study. Serum KL-6 was measured via ELISA and then Spearman correlation analysis was used to analysing their association. Subsequent the receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to estimate the diagnostic value of UA in RA-ILD and UIP pattern of RA-ILD. HRCT and pulmonary function tests (PFT) were performed to evaluated the characteristics and pulmonary findings of RA patients. Furtherly, we validated the effect of UA on the EMT and the expression of cytokines in A549 cells. Results: Compared with healthy controls (HC), UA levels in serum was significantly higher in RA group (262.25±91.94 vs. 234.69±54.78µmol/L, P<0.01). Spearman correlation analysis revealed associations of SUA with risk factors of RA, including RF, anti-CCP, CRP and ESR (r=0.37, p=0.02; r=0.48, p<0.01; r=0.26, p<0.01; r=0.27, p<0.01). And higher UA was measured both in serum (291.81±102.42 vs. 252.38±6.15µmol/L, P<0.01) and BALF (393.3±222.6 vs. 204.0±120.3µmol/L, p<0.01) of RA-ILD patients, particularly those with UIP pattern (475.58±249.28 vs. 262.86±103.45µmol/L, p<0.01; 393.3±222.6 vs. 204.0±120.3µmol/L, p<0.01). Meanwhile, the correlation between the level of UA in serum and BALF and serum KL-6 concentration in RA were also significant (r=0.59, p<0.01; r=0.43, p<0.01). Also, the negative correlations of UA level, both in serum and BALF, with lung function parameters including FEV1/FVC and FEV1% predicted were measured (r=-0.78; r=-0.87, p<0.01). In the ROC curve analysis of AUC, the AUC value of UA was 0.76 (95%CI=0.66-0.87, p<0.01). The sensitivity and specificity were 60% and 92%, respectively. The vitro experiment showed that UA stimulated the EMT in A549 cells, as well as induced the expression of cytokines, such as IL-1, IL-6 and TGF-β, in lung epithelial cell.Conclusions: This study suggests that UA is correlated with the ILD in RA. Particularly, the higher UA levels may be related to UIP, a pattern with worse prognosis, in patients with ILD. Therefore, UA may be an important contributing factor to the pathogenesis of RA-ILD.

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14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.141385 ◽

2015 ◽

Vol 42 (9) ◽

pp. 1587-1594 ◽

Cited By ~ 13

Author(s):

Walter P. Maksymowych ◽

Gilles Boire ◽

Dirkjan van Schaardenburg ◽

Stephanie Wichuk ◽

Samina Turk ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Early Rheumatoid Arthritis ◽

Roc Curve ◽

Area Under The Curve ◽

Roc Curves ◽

Healthy Controls ◽

Likelihood Ratios ◽

Roc Curve Analysis ◽

Diagnostic Use ◽

Early Ra

Objective.To describe the expression and diagnostic use of 14-3-3η autoantibodies in early rheumatoid arthritis (RA).Methods.14-3-3η autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with established RA, 55 healthy, 70 autoimmune, and 126 other non-RA arthropathy controls). 14-3-3η protein levels were determined in an earlier analysis. Two-tailed Student t tests and Mann-Whitney U tests compared differences among groups. Receiver-operator characteristic (ROC) curves were generated and diagnostic performance was estimated by area under the curve (AUC), as well as specificity, sensitivity, and likelihood ratios (LR) for optimal cutoffs.Results.Median serum 14-3-3η autoantibody concentrations were significantly higher (p < 0.0001) in patients with early RA (525 U/ml) when compared with healthy controls (235 U/ml), disease controls (274 U/ml), autoimmune disease controls (274 U/ml), patients with osteoarthritis (259 U/ml), and all controls (265 U/ml). ROC curve analysis comparing early RA with healthy controls demonstrated a significant (p < 0.0001) AUC of 0.90 (95% CI 0.85–0.95). At an optimal cutoff of ≥ 380 U/ml, the ROC curve yielded a sensitivity of 73%, a specificity of 91%, and a positive LR of 8.0. Adding 14-3-3η autoantibodies to 14-3-3η protein positivity enhanced the identification of patients with early RA from 59% to 90%; addition of 14-3-3η autoantibodies to anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) increased identification from 72% to 92%. Seventy-two percent of RF- and ACPA-seronegative patients were positive for 14-3-3η autoantibodies.Conclusion.14-3-3η autoantibodies, alone and in combination with the 14-3-3η protein, RF, and/or ACPA identified most patients with early RA.

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S100A1 as a potential biomarker for the diagnosis of patients with acute aortic dissection

Journal of International Medical Research ◽

10.1177/03000605211004512 ◽

2021 ◽

Vol 49 (4) ◽

pp. 030006052110045

Author(s):

Chenjun Han ◽

Qiang Liu ◽

Yuanmin Li ◽

Wangfu Zang ◽

Jian Zhou

Keyword(s):

Logistic Regression ◽

Aortic Dissection ◽

Roc Curve ◽

Acute Aortic Dissection ◽

Troponin T ◽

Area Under The Curve ◽

Hospital Death ◽

Clinical Value ◽

Roc Curve Analysis ◽

Potential Biomarker

Objective Acute aortic dissection (AAD) is a common life-threatening cardiovascular disease. This retrospective study was conducted to analyze the plasma concentration of S100A1 and its diagnostic value for AAD through receiver operating characteristic (ROC) curve and logistic regression analyses. Methods Seventy-eight patients with AAD and 77 healthy controls were included, and the relevant clinical data for each group were collected. According to the Stanford classification, the AAD patients were divided into types A and B. The plasma levels of S100A1, D-dimer, hypersensitive C-reactive protein, and cardiac troponin T were detected by enzyme-linked immunosorbent assays. Results The S100A1 concentrations in the healthy control, Stanford A, and Stanford B groups were 0.7 ± 0.6, 4.9 ± 2.6, and 3.5 ± 2.2 ng/mL, respectively. The concentration of S100A1 was increased in patients with AAD complicated with aortic regurgitation, pericardial effusion, or in-hospital death. ROC curve analysis showed that the area under the curve was 0.89. Logistic regression analysis revealed that the S100A1 level was an important risk factor for the development of AAD. Conclusion Plasma S100A1 is significantly elevated in patients with AAD, and its concentration has potential clinical value for diagnosing AAD.

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Expression Levels of MicroRNA-125b in Serum Exosomes of Patients with Asthma of Different Severity and its Diagnostic Significance

Current Drug Metabolism ◽

10.2174/1389200220666191021100001 ◽

2019 ◽

Vol 20 (10) ◽

pp. 781-784 ◽

Cited By ~ 1

Author(s):

Meizhen Zhao ◽

Li Juanjuan ◽

Fan Weijia ◽

Xie Jing ◽

Huang Qiuhua ◽

...

Keyword(s):

Correlation Analysis ◽

Roc Curve ◽

Quantitative Polymerase Chain Reaction ◽

Persistent Asthma ◽

Asthma Severity ◽

Control Group ◽

Spearman Correlation ◽

Diagnostic Efficacy ◽

Expression Levels ◽

Serum Exosomes

Background: This study aimed to investigate the expression levels of microRNA (miRNA)-125b in serum exosomes and its diagnostic efficacy for asthma severity. Methods: The study included 80 patients with untreated asthma and 80 healthy volunteers. The patients were divided into 4 groups according to disease severity: 20 with the intermittent state, 20 with the mildly persistent state, 20 with the moderately persistent state, and 20 with the severely persistent state. The expression levels of miRNA-125b in serum exosomes of each group were detected using a quantitative polymerase chain reaction and compared. The Spearman correlation analysis was used to study the correlation between the expression levels of miRNA-125b in serum exosomes and asthma severity. The diagnostic efficacy of the expression levels of miRNA-125b in exosomes for asthma severity was evaluated using the Receiver Operating Characteristic (ROC) curve. Results: The expression levels of miRNA-125b in serum exosomes of patients with intermittent, mildly persistent, moderately persistent, and severely persistent asthma were all higher than those in the healthy control group, with statistically significant differences. The expression levels of miRNA-125b were also statistically significantly different among patients in each group. The Spearman correlation analysis showed a positive correlation of the relative expression of miRNA-125b in serum exosomes with asthma severity. The area under the ROC curve of the diagnostic efficacy of miRNA-125b in serum exosomes for patients with intermittent, mildly, moderately, and severely persistent asthma was 0.7770, 0.8573, 0.9111, and 0.9995, respectively. Conclusion: The expression levels of miRNA-125b in serum exosomes had a high diagnostic efficacy and might serve as a noninvasive diagnostic marker for asthma severity.

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Is There Any Association Between Uric Acid to High-density Lipoprotein Cholesterol Ratio and Erectile Dysfunction?

Grand Journal of Urology ◽

10.5222/gju.2021.00719 ◽

2021 ◽

Author(s):

Dilay Karabulut ◽

Mustafa Gürkan Yenice

Keyword(s):

Uric Acid ◽

Erectile Dysfunction ◽

High Density Lipoprotein ◽

Roc Curve ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Roc Curve Analysis ◽

Cholesterol Ratio ◽

Group 3

Objective: Elevated uric acid (UA) and low levels of high-density lipoprotein (HDL) cholesterol are associated with cardiovascular events and mortality. Erectile dysfunction (ED) has been considered an early marker of cardiovascular disease (CVD). Therefore, this study aimed to investigate the uric acid/ HDL ratio (UHR) as a nowel marker in patients with ED. Materials and Methods: The study included 147 patients with a mean age of 50 years (range 32-76 years). Retrospective analyses were performed on the patients who were admitted to urology outpatient clinics. The laboratory parameter results were retrieved from the hospital medical records, and the UHR value was calculated. Patients were categorized into three groups according to the International Index of Erectile Function (IIEF) score. UHR was compared between groups, and its predictive value was evaluated using regression analysis and ROC curve analysis. Results: Age was found to be significantly different in all three groups (Groups 1-2, p=0.001; Groups 1-3, p=0.000; Groups 2-3, p=0.001). It was observed that the degree of ED increased with age. The values of UA and HDL were similar in all groups (p>0.05). In contrast, the UHR value was statistically significantly higher 0.15 (0.083-0.288, p =0.047) in the moderate-severe ED (Group 3). ROC curve analyses revealed that UHR predicted severe ED (IIEF 5-11) with 42.9% sensitivity and 87.3% specificity (AUC:0.66, CI 95% 0.538-0.781, p=0.019). Conclusion: UHR may serve as a severe ED indicator in patients admitted to the cardiology outpatient clinic since it has a significant association with a low IIEF score.

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Association among B lymphocyte subset and rheumatoid arthritis in a Chinese population

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02883-8 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Haiyan You ◽

Mengwei Cheng ◽

Cui Ma ◽

Wenjuan Zheng ◽

Yu Jiang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Healthy Subjects ◽

B Lymphocyte ◽

Lymphocyte Subsets ◽

Characteristic Curve ◽

Area Under The Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Roc Curve Analysis ◽

Autoantibody Production ◽

Plasma Cytokines

Abstract Background and aim Autoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters. Methods In total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction. Results The percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing RA was 0.831 (95% CI 0.748 ~ 0.915), the specificity was 91.4%, and the sensitivity was 67.5%. The AUC predicted by the combination of plasmablast and anti-CCP for active RA patients was 0.760, which was higher than that of plasmablast and anti-CCP. Conclusion In conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA.

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Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients

Cellular Physiology and Biochemistry ◽

10.1159/000477883 ◽

2017 ◽

Vol 42 (2) ◽

pp. 651-659 ◽

Cited By ~ 59

Author(s):

Qingqing Ouyang ◽

Jing Wu ◽

Zhenlan Jiang ◽

Jinjun Zhao ◽

Ran Wang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Peripheral Blood Mononuclear Cells ◽

Roc Curve ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Circular Rnas ◽

Screening Methods ◽

Roc Curve Analysis ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Background/Aims: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening. Methods: We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value. Results: We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030). Conclusions: This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.

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A new “ASAP Scoring System and Risk Table” in patients with Atypical Small Acinar Proliferation (ASAP) to predict the second prostate biopsy outcomes

10.22541/au.162315970.02842740/v1 ◽

2021 ◽

Author(s):

Caner Ediz ◽

Serkan Akan ◽

Neslihan Kaya Terzi ◽

Aysenur Ihvan

Keyword(s):

Prostate Biopsy ◽

Roc Curve ◽

Scoring System ◽

Risk Group ◽

Area Under The Curve ◽

Threshold Value ◽

Roc Curve Analysis ◽

Atypical Small Acinar Proliferation ◽

The Mean ◽

Density Assessment

Background: To discuss the necessity of the second prostate biopsy in the patients with atypical small acinar proliferation (ASAP) and to develop a scoring system and risk table as a new re-biopsy criteria. Methods: 2845 patients who were performed transrectal ultrasonography-guided prostate biopsy between January 2008 and May 2019 were evaluated. 128 patients, whose data were reached, were enrolled into the study. Before the first and the second biopsy, tPSA, fPSA, f/tPSA rate and PSA-Density assessment and changes in these parameters between the two biopsies were recorded. “ASAP Scoring System and risk table” (ASS-RT) was evaluated before the second biopsy. Results: The mean age of 128 patients with ASAP was 62.9±7.8 years. The ASS-RT scores of the patients with PCa were statistically significantly higher than the patients with non-PCa (p: 0.001). In the ROC curve analysis of ASS-RT, area under the curve was 0.804 and the standard error was 0.04. The area under the ROC curve was significantly higher than 0.5 (p:0.001). The cut-off point of ASS-RT score in diagnosis of malignancy was ≥ 7. The sensitivity of this value was found to be 60.8% and its specificity as 80.5%. Conclusions: The threshold value for the ASS-RT score may be used as 7 and the second biopsy may be performed immediately to patients over this value. We think that there may be no need for a second biopsy if the ASS-RT score under the 7 (especially low-risk group) before the second biopsy.

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Evaluation of prediction score of contrast-induced nephropathy in inpatients undergone to digital or CT angiography

REVISTA CIÊNCIAS EM SAÚDE ◽

10.21876/rcshci.v10i3.974 ◽

2020 ◽

Vol 10 (3) ◽

pp. 78-84

Author(s):

Seleno Glauber de Jesus-Silva ◽

Ana Elisa Chaves ◽

Caio Augusto Alves Maciel ◽

Edson Eziel Ferreira Scotini ◽

Pablo Girardelli Mendonça Mesquita ◽

...

Keyword(s):

Computed Tomography ◽

Roc Curve ◽

Computed Tomography Angiography ◽

Score Test ◽

Area Under The Curve ◽

Roc Curve Analysis ◽

Contrast Induced Nephropathy ◽

Mean Values ◽

Iodinated Contrast ◽

The Mean

Objectives: To assess the incidence of contrast-induced nephropathy (CIN) and determine the Mehran Score's (MS) ability to predict CIN in patients undergoing digital angiography or computed tomography angiography. Methods: 252 medical records of inpatients who underwent DA or CTA over 28 months in a quaternary hospital were reviewed. CIN was defined as serum creatinine> 0.5 mg / dL or > 25% increase in baseline creatinine, 48 h after administration of iodinated contrast. The ROC curve and the area under the curve (AUC) were used as a score test. Results: The majority (159; 63.1%) were male, and the average age was 60.4 years. Anemia, diabetes mellitus, and age > 75 years were the most prevalent factors. The incidence of CIN was 17.8% (n = 45). There was a decrease in the mean values of creatinine pre and post among patients who did not suffer CIN (1.38 ± 1.22 vs 1.19 ± 0.89; t = 3.433; p = 0.0007), while among patients who suffering CIN, the mean increase was 1.03 mg / dL (1.43 ± 1.48 vs 2.46 ± 2.35 mg / dL; t = 5.44; p = 0.117). The ROC curve analysis identified a low correlation between MS and the occurrence of CIN (AUC = 0.506). Conclusion: The incidence of CIN in hospitalized patients undergoing angiography or computed tomography angiography was high. The EM did not allow the prediction of NIC.

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Association Among B Lymphocyte Subset and Rheumatoid Arthritis in A Chinese Population

10.21203/rs.3.rs-793561/v1 ◽

2021 ◽

Author(s):

Haiyan You ◽

Mengwei Cheng ◽

Cui Ma ◽

Wenjuan Zheng ◽

Yu Jiang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Healthy Subjects ◽

B Lymphocyte ◽

Lymphocyte Subsets ◽

Characteristic Curve ◽

Area Under The Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Roc Curve Analysis ◽

Autoantibody Production ◽

Plasma Cytokines

Abstract Background and aim: Autoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters. Methods In total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction. Results The percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing APN was 0.831 (95% CI 0.748ཞ0.915), the specificity was 91.4%, and the sensitivity was 67.5%. Conclusion In conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA.

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Using Circ-ANAPC7 as a Novel Type of Biomarker in the Monitoring of Acute Myeloid Leukemia

Acta Haematologica ◽

10.1159/000520446 ◽

2021 ◽

pp. 1-7

Author(s):

Ying Shen ◽

Yachun Jia ◽

Ru Zhang ◽

Hongli Chen ◽

Yuandong Feng ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Roc Curve ◽

Myeloid Leukemia ◽

Area Under The Curve ◽

Diagnostic Value ◽

Circular Rnas ◽

Transcriptional Level ◽

Roc Curve Analysis ◽

Cell Counts ◽

Acute Myeloid

Introduction: Circular RNAs (circRNAs) are a novel class of RNAs which occupy gene expression at the transcriptional or post-transcriptional level, involve in many physiological processes, and participate in many diseases, especially in cancer. Our previous study showed 1 altered circRNA named circ-anaphase promoting complex subunit 7 (ANAPC7) that was upregulated in acute myeloid leukemia (AML). To further clear the expression and clinical significance of circ-ANAPC7, we enlarged the sample size and illuminated the diagnostic and monitoring value of circ-ANAPC7 in AML. Methods: Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was supposed to confirm the expression of circ-ANAPC7 of AML patients. We assessed the correlation of circ-ANAPC7 and clinical variables using the Spearman correlation test. The receiver operating characteristic (ROC) curve was carried out to evaluate the diagnostic value. Results: Circ-ANAPC7 was first found to be upregulated in AML, and its expression was correlated to white blood cell counts in peripheral blood and blast percentage in bone marrow. ROC curve analysis revealed that circ-ANAPC7 has a significant value of auxiliary AML diagnosis (area under the curve = 0.915, p < 0.001). Furthermore, the expression level of circ-ANAPC7 was changed accompanied with disease condition transformation. Conclusion: Circ-ANAPC7 was upregulated in newly diagnosed and relapsed AML. It may serve as potential biomarkers for AML patient’s diagnosis and monitoring.

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