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      Serum levels of interleukins and S100A8/A9 correlate with clinical severity in patients with dermatomyositis-associated interstitial lung disease

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          Abstract

          Background

          Dermatomyositis (DM) is a systemic autoimmune inflammatory disorder that affects primarily skin, muscle and lung, frequently associated with interstitial lung disease (ILD). The objective of this study is to investigate the association between serum cytokines and clinical severity in patients with DM-ILD.

          Methods

          Serum samples of 30 healthy controls, 14 DM patients without ILD and 40 DM patients with ILD were collected. Serum S100A8/A9 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) and levels of interleukins were measured by cytometric beads array (CBA). Then we performed multivariate logistic regression analysis to determine factors independently associated with ILD development.

          Results

          Serum IL-4, IL-6 and S100A8/A9 levels were significantly higher in DM patients with ILD than those in healthy controls ( p = 0.0013, 0.0017 and < 0.0001, respectively). Serum IL-10 level of patients was dramatically lower than that in controls ( p = 0.0001). In DM patients, the levels were significantly higher in patients with A/SIP than in those with CIP ( p = 0.0046, 0.0339 and 0.0133) or without ILD ( p = 0.0165, 0.0370 and < 0.0001). IL-4 ( r = 0.1171, p = 0.0040), IL-6 ( r = 0.1174, p = 0.0040) and IL-10 ( r = − 0.1829, p = 0.0003) were significantly correlated with S100A8/A9 in DM-ILD patients. S100A8/A9 was significantly correlated with high-resolution computed tomography (HRCT) ( r = 0.1642, p = 0.0157) and lung function (DLCO%: r = − 0.2066, p = 0.0061, FVC%: r = − 0.2156, p = 0.0050). Moreover, logistic regression analysis revealed that S100A8/A9 levels were independently associated with ILD development in DM patients ( p = 0.004).

          Conclusions

          Serum level of S100A8/A9 may be a valuable predictor for assessing the clinical severity of DM-ILD patients. Serum IL-4, IL-6 and IL-10 levels were highly correlated with S100A8/A9, so these cytokines may play a synergistic effect on the progression of DM-ILD.

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          Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells.

          P Freemont, Matthew Bennett, Jack M. Gorman … (1991)
          In this report we describe the biochemical characterization of neutrophil and monocyte p8 and p14. Together the two proteins comprise approximately 45% of cytosolic protein in neutrophils and approximately 40-fold less in monocytes. They fractionated together in several chromatographic procedures and were found to exist as a noncovalently associated complex with a stoichiometry of 1:1, named p8,14. Cross-linking experiments showed p8,14 to form heterodimers under conditions simulating the cytosol. An apparent molecular mass of 35,000 daltons was obtained for the p8,14 complex in molecular sizing experiments which suggests the presence of modifications or distinctive structural features. Two major forms of p14 can be identified by two-dimensional gel electrophoresis, both of which form heterodimers with p8. The lower molecular weight variant of p14 lacks Cys-3 (Met-Thr-Cys-Lys-Met...) suggesting that differing translational start sites account for these two forms of p14. A protocol has been devised for the rapid purification of milligram quantities of p8 and p14 from neutrophil cytosol using fast-protein liquid chromatography.
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            Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules.

            Johannes Roth, Thomas Vogl, Clemens Sorg … (2003)
            Three members of the S100 family of calcium-binding proteins comprise a new group of proinflammatory molecules released by phagocytes. A novel inflammatory syndrome defined by extraordinarily high expression of S100A8 and S100A9 confirmed recent observations in vitro demonstrating a role of these proteins during recruitment of leukocytes. S100A12 directly activates endothelial cells, mononuclear phagocytes and lymphocytes through interaction with the receptor for advanced glycation end products. Thus, these S100-proteins are attractive targets to modulate inflammation.
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              Short-term and long-term outcomes of interstitial lung disease in polymyositis and dermatomyositis: a series of 107 patients.

              I Marié, J Menard, S Dominique … (2011)
              This study was undertaken to assess the characteristics and outcome of interstitial lung disease (ILD) in polymyositis/dermatomyositis (PM/DM) and to determine variables predictive of ILD deterioration in PM/DM. Among 348 consecutive patients with PM/DM, 107 patients with ILD were identified by medical records search in 4 medical centers. All patients underwent pulmonary function tests (PFTs) and pulmonary high-resolution computed tomography (HRCT) scan. ILD onset preceded PM/DM clinical manifestations in 20 patients, was identified concurrently with PM/DM in 69 patients, and occurred after PM/DM onset in 18 patients. Patients with ILD could be divided into 3 groups according to their presenting lung manifestations: patients with acute lung disease (n = 20), patients with progressive-course lung signs (n = 55), and asymptomatic patients with abnormalities consistent with ILD evident on PFTs and HRCT scan (n = 32). We observed that 32.7% of the patients had resolution of pulmonary disorders, whereas 15.9% experienced ILD deterioration. Factors that predicted a poor ILD prognosis were older age, symptomatic ILD, lower values of vital capacity and diffusing capacity for carbon monoxide, a pattern of usual interstitial pneumonia on HRCT scan and lung biopsy, and steroid-refractory ILD. The mortality rate was higher in patients with ILD deterioration than in those without ILD deterioration (47.1% versus 3.3%). Our findings indicate that ILD results in high morbidity in PM/DM. Our findings also suggest that more aggressive therapy may be required in PM/DM patients presenting with factors predictive of poor ILD outcome. Copyright © 2011 by the American College of Rheumatology.
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                Author and article information

                Contributors
                Xiaoming Tan: tanxiaomingfsh@163.com
                Qing Wei:
                ORCID: http://orcid.org/0000-0002-8437-1145
                weiqingjn@126.com
                Journal
                Journal ID (nlm-ta): BMC Pulm Med
                Journal ID (iso-abbrev): BMC Pulm Med
                Title: BMC Pulmonary Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2466
                Publication date (Electronic): 17 July 2020
                Publication date PMC-release: 17 July 2020
                Publication date Collection: 2020
                Volume: 20
                Electronic Location Identifier: 196
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Pulmonology, , Renji Hospital South Campus, Shanghai Jiaotong University School of Medicine, ; Shanghai, People’s Republic of China
                [2 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Rheumatology, , Renji Hospital South Campus, Shanghai Jiaotong University School of Medicine, ; Shanghai, People’s Republic of China
                [3 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Laboratory Medicine, , Renji Hospital South Campus, Shanghai Jiaotong University School of Medicine, ; Shanghai, People’s Republic of China
                Author information
                http://orcid.org/0000-0002-8437-1145
                Article
                Publisher ID: 1226
                DOI: 10.1186/s12890-020-01226-3
                PMC ID: 7368671
                PubMed ID: 32680574
                SO-VID: f6020d5a-33b8-4ed9-80fa-6d0aabf7a283
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 3 September 2019
                Date accepted : 2 July 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100011471, Shanghai Minhang Health And Family Planning Commission;
                Award ID: 20184Y0189
                Award Recipient :
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2020

                ScienceOpen disciplines: Respiratory medicine
                Keywords: dermatomyositis,interstitial lung disease,s100a8/a9,interleukin
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: dermatomyositis, interstitial lung disease, s100a8/a9, interleukin

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