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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.
Liu et al. (Sat,) studied this question.