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      Serum Amyloid A Is a Biomarker of Disease Activity and Health-Related Quality-of-Life in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

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          Abstract

          Serum amyloid A (SAA) is one of the acute phase proteins synthesized in hepatocytes and secreted by various inflammation or infectious stimuli. We investigated the clinical implication of measuring SAA in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). Seventy-five patients who had been classified as AAV and enrolled in our prospective observational cohort for AAV patients were included. Clinical and laboratory data were obtained on the day of blood sampling, and SAA was measured by ELISA kits. Birmingham Vasculitis Activity Score (BVAS) and Short-Form 36-Item Health Survey (SF-36) were assessed for disease activity and health-related quality-of-life (HRQoL) measures. We stratified patients into having high BVAS when the BVAS was over the median values, and those with either low SF-36 PCS or low SF-36 MCS were defined as having poor HRQoL. Multivariate logistic regression analysis was conducted to estimate independent predictors of high BVAS. The relative risk (RR) was analyzed using the contingency tables and the chi-squared test. SAA was positively correlated with BVAS ( r = 0.642) and FFS ( r = 0.367) and was inversely correlated with both the SF-36 physical component summary ( r = −0.456) and mental component summary scores ( r = −0.394). Furthermore, SAA was significantly correlated with acute phase reactants ESR ( r = 0.611) and CRP ( r = 0.629). Patients with high BVAS exhibited significantly higher SAA than those with low BVAS (1317.1 ng/mL vs. 423.1 ng/mL). In multivariable logistic regression analysis, serum albumin (odds ratio (OR) 0.132) and SAA > 1173.6 ng/mL (OR 15.132) were independently associated with high BVAS. The risk of having high BVAS and poor HRQoL in patients with SAA > 1173.6 ng/mL was higher than in those with SAA ≤ 1173.6 ng/mL (RR 3.419 and 1.493). Our results suggest that SAA might be a useful biomarker in assessing disease activity and HRQoL in AAV.

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          Most cited references32

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          2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

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            Understanding diagnostic tests 3: Receiver operating characteristic curves.

            The results of many clinical tests are quantitative and are provided on a continuous scale. To help decide the presence or absence of disease, a cut-off point for 'normal' or 'abnormal' is chosen. The sensitivity and specificity of a test vary according to the level that is chosen as the cut-off point. The receiver operating characteristic (ROC) curve, a graphical technique for describing and comparing the accuracy of diagnostic tests, is obtained by plotting the sensitivity of a test on the y axis against 1-specificity on the x axis. Two methods commonly used to establish the optimal cut-off point include the point on the ROC curve closest to (0, 1) and the Youden index. The area under the ROC curve provides a measure of the overall performance of a diagnostic test. In this paper, the author explains how the ROC curve can be used to select optimal cut-off points for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of tests. The ROC curve is obtained by calculating the sensitivity and specificity of a test at every possible cut-off point, and plotting sensitivity against 1-specificity. The curve may be used to select optimal cut-off values for a test result, to assess the diagnostic accuracy of a test, and to compare the usefulness of different tests.
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              Modification and validation of the Birmingham Vasculitis Activity Score (version 3).

              Comprehensive multisystem clinical assessment using the Birmingham Vasculitis Activity score (BVAS) is widely used in therapeutic studies of systemic vasculitis. Extensive use suggested a need to revise the instrument. The previous version of BVAS has been revised, according to usage and reviewed by an expert committee. To modify and validate version 3 of the BVAS in patients with systemic vasculitis. The new version of BVAS was tested in a prospective cross-sectional study of patients with vasculitis. The number of items was reduced from 66 to 56. The subscores for new/worse disease and persistent disease were unified. In 313 patients with systemic vasculitis, BVAS(v.3) correlated with treatment decision (Spearman's r(s) = 0.66, 95% CI 0.59 to 0.72), BVAS1 of version 2 (r(s) = 0.94, 95% CI 0.92 to 0.96), BVAS2 of version 2 in patients with persistent disease (r(s) = 0.60, 95% CI 0.21 to 0.83), C-reactive protein levels (r(s) = 0.43, 95% CI 0.31 to 0.54), physician's global assessment (r(s) = 0.91, 95% CI 0.89 to 0.93) and vasculitis activity index (r(s) = 0.88, 95% CI 0.86 to 0.91). The intraclass correlation coefficients for reproducibility and repeatability were 0.96 (95% CI 0.95 to 0.97) and 0.96 (95% CI 0.92 to 0.97), respectively. In 39 patients assessed at diagnosis and again at 3 months, the BVAS(v.3) fell by 17 (95% CI 15 to 19) units (p<0.001, paired t test). BVAS(v.3) demonstrates convergence with BVAS(v.2), treatment decision, physician global assessment of disease activity, vasculitis activity index and C-reactive protein. It is repeatable, reproducible and sensitive to change. The new version of BVAS is validated for assessment of systemic vasculitis.
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                Author and article information

                Contributors
                Journal
                Dis Markers
                Dis Markers
                DM
                Disease Markers
                Hindawi
                0278-0240
                1875-8630
                2020
                16 December 2020
                : 2020
                : 8847306
                Affiliations
                1Department of Medical Science, BK21 Plus Project, Yonsei University College of Medicine, Seoul, Republic of Korea
                2Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
                3Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
                Author notes

                Academic Editor: Paolo Cameli

                Author information
                https://orcid.org/0000-0002-8038-3341
                Article
                10.1155/2020/8847306
                7787824
                33488845
                3b0186c7-4f4a-48a4-bf5c-3b8230bed60a
                Copyright © 2020 Taejun Yoon et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 April 2020
                : 26 November 2020
                : 4 December 2020
                Funding
                Funded by: Ministry of Health and Welfare
                Award ID: HI14C1324
                Funded by: Korea Health Industry Development Institute
                Funded by: Yonsei University College of Medicine
                Award ID: 6-2019-0184
                Categories
                Research Article

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