Correlation between lung microecology and immunity in patients with anti-MDA5 antibody-positive dermatomyositis combined with interstitial lung disease: protocol for a prospective, multicentre cohort study

Correlation between lung microecology and immunity in patients with anti-MDA5 antibody-positive dermatomyositis combined with interstitial lung disease: protocol for a prospective, multicentre cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Correlation between lung microecology and immunity in patients with anti-MDA5 antibody-positive dermatomyositis combined with interstitial lung disease: protocol for a prospective, multicentre cohort study Shuzi Liu, Zhimei Duan, Kaifei Wang, Gui luo, Xiaojian Ji, Ye Hu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4305936/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5 + DM) may be associated with interstitial lung disease (ILD), particularly rapidly progressive interstitial lung disease (RP-ILD). It leads to a poor prognosis and mortality rate of approximately 40%–90%. Patients with ILD or RP-ILD are always infected with various pathogens in the lungs. However, the aetiology and pathogenesis of the susceptibility of patients with anti-MDA5 + DM to ILD or RP-ILD remain largely unknown. Multiple studies have confirmed the existence of pulmonary microecology in respiratory diseases related to host immune response. However, the relationship and mechanism underlying the immune response and pulmonary infection in patients with anti-MDA5 + DM have not been reported. Therefore, this study aimed to explore the mechanism of ILD/RP-ILD susceptibility in patients with anti-MDA5 + DM through the relationship between the pulmonary microbiome, host immune response, and the presence or absence of concurrent RP-ILD. Methods /design We will enrol 50 patients with anti-MDA5 + DM from multiple medical centres, who will be divided into three groups: anti-MDA5 + DM with RP-ILD, anti-MDA5 + DM with non-RP-ILD, and anti-MDA5 + DM without ILD. Patients will be followed up for 6 months, with three clinical samples and data collected. We will identify pathogenic microorganisms and host genome metagenomics through next-generation sequencing (mNGS) and metagenomics third-generation sequencing (mTGS), and analyse whether identical or similar gene fragments of MDA5 are present in the genes of patients' lung microbiota to explore the possible relationship between pathogen genes and MDA5 antibody production. Additionally, we will analyse the host immune function status, inflammatory response status, and infection stage by immune cell counting, single-cell sequencing, metabolomics, proteomics, and flow cytometry. Discussion The study aims to conduct a comprehensive assessment of the host immune function status after infection and explore the relationship between the lung microbiome, host immune function status, and RP-ILD. Finally, we expect that the results of this study will potentially provide an early warning for RP-ILD development in patients with anti-MDA5 + DM and lay the foundation for future differentiated treatments targeting opportunistic pathogens and/or host immune factors. Trial registration ClinicalTrials. gov, identifier: NCT06203249. Registered on December 28, 2023. Anti-MDA5+ dermatomyositis Interstitial lung disease Lung microecology Immunity Cohort study Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4305936","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":294456762,"identity":"b03bfa4a-e1ca-41fb-9cba-17c3285bc473","order_by":0,"name":"Shuzi Liu","email":"","orcid":"","institution":"Chinese People's Liberation Army (PLA) General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shuzi","middleName":"","lastName":"Liu","suffix":""},{"id":294456763,"identity":"cc4131c2-f37e-4854-ab14-e2597a0ebb47","order_by":1,"name":"Zhimei Duan","email":"","orcid":"","institution":"Chinese People's Liberation Army (PLA) General 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competing interests reported.","formattedTitle":"Correlation between lung microecology and immunity in patients with anti-MDA5 antibody-positive dermatomyositis combined with interstitial lung disease: protocol for a prospective, multicentre cohort study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Anti-MDA5+ dermatomyositis, Interstitial lung disease, Lung microecology, Immunity, Cohort study","lastPublishedDoi":"10.21203/rs.3.rs-4305936/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4305936/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u003c/p\u003e\n\u003cp\u003eAnti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM) may be associated with interstitial lung disease (ILD), particularly rapidly progressive interstitial lung disease (RP-ILD). It leads to a poor prognosis and mortality rate of approximately 40%–90%. Patients with ILD or RP-ILD are always infected with various pathogens in the lungs. However, the aetiology and pathogenesis of the susceptibility of patients with anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM to ILD or RP-ILD remain largely unknown. Multiple studies have confirmed the existence of pulmonary microecology in respiratory diseases related to host immune response. However, the relationship and mechanism underlying the immune response and pulmonary infection in patients with anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM have not been reported. Therefore, this study aimed to explore the mechanism of ILD/RP-ILD susceptibility in patients with anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM through the relationship between the pulmonary microbiome, host immune response, and the presence or absence of concurrent RP-ILD.\u003c/p\u003e\n\u003cp\u003eMethods /design\u003c/p\u003e\n\u003cp\u003eWe will enrol 50 patients with anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM from multiple medical centres, who will be divided into three groups: anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM with RP-ILD, anti-MDA5\u003csup\u003e+ \u003c/sup\u003eDM with non-RP-ILD, and anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM without ILD. Patients will be followed up for 6 months, with three clinical samples and data collected. We will identify pathogenic microorganisms and host genome metagenomics through next-generation sequencing (mNGS) and metagenomics third-generation sequencing (mTGS), and analyse whether identical or similar gene fragments of MDA5 are present in the genes of patients' lung microbiota to explore the possible relationship between pathogen genes and MDA5 antibody production. Additionally, we will analyse the host immune function status, inflammatory response status, and infection stage by immune cell counting, single-cell sequencing, metabolomics, proteomics, and flow cytometry.\u003c/p\u003e\n\u003cp\u003eDiscussion\u003c/p\u003e\n\u003cp\u003eThe study aims to conduct a comprehensive assessment of the host immune function status after infection and explore the relationship between the lung microbiome, host immune function status, and RP-ILD. Finally, we expect that the results of this study will potentially provide an early warning for RP-ILD development in patients with anti-MDA5\u003csup\u003e+\u003c/sup\u003e DM and lay the foundation for future differentiated treatments targeting opportunistic pathogens and/or host immune factors.\u003c/p\u003e\n\u003cp\u003eTrial registration\u003c/p\u003e\n\u003cp\u003eClinicalTrials. gov, identifier: NCT06203249. 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