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      Serum Aminoacyl-tRNA Synthetase-Interacting Multifunctional Protein-1 Can Predict Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Pilot Monocentric Study

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          Abstract

          We investigated whether serum aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) could predict severe cases of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on the Birmingham vasculitis activity score (BVAS). Sixty-one patients with AAV were selected for inclusion from our prospective AAV cohort. AAV-specific indices and clinical manifestations were assessed, and laboratory tests were performed on the day of blood sampling. Patients with severe AAV were defined as those with a BVAS higher than the lower limit of the highest tertile of BVAS (BVAS ≥ 12). We measured serum AIMP1 levels of the stored serum samples. A total of 20 (32.8%) and 41 (67.2%) patients were classified as having severe and nonsevere AAV according to the cut-off of BVAS ≥ 12. Patients with severe AAV showed higher frequencies of general and renal manifestations, along with ANCA positivity, and exhibited a higher mean neutrophil count, erythrocyte sedimentation rate, and C-reactive protein levels, but lower mean haemoglobin and serum albumin levels than those with nonsevere AAV. The mean serum AIMP1 level in patients with severe AAV was significantly higher than that of patients with nonsevere AIMP1 (351.1 vs. 98.4 pg/mL, p = 0.006). Multivariate logistic regression analysis including variables showing significance in univariate analyses revealed that only serum AIMP1 exhibited a significant association with severe AAV (odds ratio 1.004, p = 0.031). When we set the optimal cut-off of serum AIMP1 for severe AAV to 50.28 pg/mL, patients with severe AAV more frequently had AIMP1 levels above the cut-off than those with nonsevere AAV (80.0% vs. 31.7%, relative risk 8.615, p < 0.001). The results from our study suggest that serum AIMP1 can be used to estimate the cross-sectional severe AAV population based on the BVAS.

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          Development of the Korean version of Short-Form 36-Item Health Survey: health related QOL of healthy elderly people and elderly patients in Korea.

          The health-related QOL (HRQOL) has been used extensively in clinical and epidemiological research and health service studies. Especially, the Medical Outcome Study Short-form 36-Item Health Survey (SF-36) is a widely used health status measure. However, a Korean version has not been developed and tested yet. The purpose of this study was to develop a Korean version of the Short-form Health Survey (SF-36) for use in health related quality of life measurements for Korean elderly people. SF-36 data from 90 healthy elderly people using Social Education Service and 120 elderly patients using a day care service in Seoul, Korea, were examined. We translated SF-36 version 2.0 into Korean and assessed its reliability and validity. In the results, the content validity and discriminant validity were found to be satisfactory. Cronbach's alpha coefficients ranged from 0.9298 to 0.9383. The test-retest reliability coefficients ranged from 0.710 to 0.895. In addition, the utility was examined by testing the correlation between the health-related QOL and related factors (sex, age, motor function, ability of daily life) among the elderly people. The present findings suggested that the Korean version of SF-36 would be useful as a measure of the health related QOL in Korean elderly people.
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            Mechanisms of Disease: pathogenesis and treatment of ANCA-associated vasculitides.

            Wegener's granulomatosis and microscopic polyangiitis are idiopathic systemic vasculitides strongly associated with antineutrophil cytoplasmic autoantibodies (ANCA). In Wegener's granulomatosis, ANCA are mostly directed against proteinase 3 (PR3), whereas in microscopic polyangiitis ANCA are directed against myeloperoxidase; increases in levels of these autoantibodies precede or coincide with clinical relapses in many cases. In vitro, ANCA can further activate primed neutrophils to release reactive oxygen species and lytic enzymes, and, in conjunction with neutrophils, can damage and lyse endothelial cells. Patients with Wegener's granulomatosis or microscopic polyangiitis have an increased percentage of neutrophils that constitutively express PR3 on their membrane. These neutrophils can be stimulated by ANCA, without priming. In vivo, transfer of splenocytes from myeloperoxidase-deficient mice immunized with mouse myeloperoxidase into wild-type mice resulted in pauci-immune systemic vasculitis. A similar experiment in PR3-deficient mice did not cause significant vasculitic lesions. Together, clinical, in vitro and in vivo experimental data support a pathogenic role for ANCA in Wegener's granulomatosis and microscopic polyangiitis, although this role is more evident for myeloperoxidase-specific ANCA than for PR3-specific ANCA. Several controlled trials have led to an evidence-based approach for the treatment of ANCA-associated vasculitis, and further studies, based on new insights into pathogenesis, are in progress.
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              Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): a triad for cellular homeostasis.

              Aminoacyl-tRNA synthetases (ARSs) are highly conserved for efficient and precise translation of genetic codes. In higher eukaryotic systems, several different ARSs including glutamyl-prolyl-, isoelucyl-, leucyl-, methionyl-, glutaminyl-, lysyl-, arginyl-, and aspartyl-tRNA synthetase form a macromolecular protein complex with three nonenzymatic cofactors (AIMP1/p43, AIMP2/p38, and AIMP3/p18). Although the structure and functional implications for this complex formation are not completely understood, rapidly accumulating evidences suggest that this complex would work as a molecular hub linked to the multiple signaling pathways that involve the components of enzymes and cofactors. In this article, the roles of three nonenzymatic components of the multi-tRNA synthetase complex in the assembly of the components and in cell regulation are addressed.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2019
                20 May 2019
                : 2019
                : 7508240
                Affiliations
                1Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
                2College of Pharmacy, Ajou University, Suwon, Gyeonggi-do, Republic of Korea
                3Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
                Author notes

                Academic Editor: Lorenzo Cavagna

                Author information
                http://orcid.org/0000-0003-4695-8620
                http://orcid.org/0000-0002-8038-3341
                http://orcid.org/0000-0002-4870-2242
                Article
                10.1155/2019/7508240
                6545776
                bc82c5a3-37e8-4a06-b525-50f8b7bcade0
                Copyright © 2019 Sung Soo Ahn 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
                : 12 December 2018
                : 22 April 2019
                : 9 May 2019
                Funding
                Funded by: Yonsei University College of Medicine
                Award ID: 6-2016-0145
                Funded by: National Research Foundation of Korea
                Award ID: NRF-2017R1A2B4002968
                Categories
                Research Article

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