{ "abstract": "Background: Anti-Ro52/TRIM21 shows contradictory prognostic associations in interstitial lung disease (ILD), protective in some cohorts and adverse in others. We evaluated whether it acts as an independent predictor or a phenotypic marker and whether its effect is modified by disease subtype and myositis-specific antibodies.\n\nMethods: We retrospectively identified 538 adults with radiologically confirmed interstitial lung disease (228 anti-Ro52-positive) from a 2010–2020 single-center cohort. Cox proportional-hazards models were sequentially adjusted for demographic, smoking, malignancy, and pulmonary-function covariates. Pre-specified effect modification by connective tissue disease (CTD) status and myositis-specific antibodies was assessed by likelihood-ratio interaction tests with false-discovery-rate correction. Robustness to missing data was supported by multiple imputation ( m = 20) and a missing-not-at-random (MNAR) tipping-point analysis.\n\nResults: Ro52 positivity was associated with younger age, CTD predominance, and lower complement levels. Pre-specified effect modification was suggested: anti-Ro52 trended toward lower mortality in CTD-ILD (HR 0.73, 95% CI 0.49–1.07, P = 0.104) but did not independently increase mortality within the anti-MDA5-positive subgroup (HR 1.73, 95% CI 0.66–4.54). Instead, the adverse prognostic effect of anti-MDA5 was numerically greater among anti-Ro52-positive than Ro52-negative patients (MDA5 HR 10.57, 95% CI 3.60–31.03 vs. 2.56, 95% CI 0.97–6.74), although the formal interaction term did not reach statistical significance ( P = 0.055). The fully adjusted (Model 6) HR was 0.72 (95% CI 0.52–0.99; P = 0.045); further adjustment for CTD status (Model 7) attenuated the association to non-significance (HR 0.75, 95% CI 0.54–1.04, P = 0.091), and IPCW weighting and time-varying-age analyses were likewise non-significant; malignancy independently predicted mortality (HR 1.81, 95% CI 1.15–2.88; P = 0.012).\n\nConclusion: Anti-Ro52 is a context-dependent phenotypic marker of immune-mediated ILD, not a universal prognostic biomarker. Its prognostic association is heterogeneous across ILD phenotypes: it is not independently protective in CTD-ILD (adjusted HR 0.73, P = 0.104), whereas the adverse prognostic effect of anti-MDA5 was numerically greater among anti-Ro52-positive than Ro52-negative patients (MDA5 HR 10.57 vs. 2.56), although this interaction did not reach statistical significance ( P = 0.055); CTD-status adjustment similarly attenuated the Ro52 association (HR 0.75, P = 0.091). These findings support stratified prognostic models integrating Ro52 with autoantibody and disease-subtype context.", "abstract_shown": true, "affiliations": [ "Department of General Intensive Care Unit, the Second Affiliated Hospital of Zhejiang University School of Medicine", "Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education", "Department of Rheumatology, the Second Affiliated Hospital of Zhejiang University School of Medicine", "Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine", "Department of Pharmacy, the Second Affiliated Hospital of Zhejiang University School of Medicine", "Department of Rheumatology, the First Affiliated Hospital of Ningbo University", "Department of Rheumatology, Ningbo Yinzhou No.2 Hospital", "Department of Radiology, the Second Affiliated Hospital of Zhejiang University School of Medicine", "Department of Clinical Epidemiology & Biostatistics, the Second Affiliated Hospital of Zhejiang University School of Medicine", "Department of Critical Care Medicine, The First People’s Hospital of Jingdezhen" ], "article_type": "research article", "arxiv": null, "author_total": 11, "authors": [ { "affs": [ 0, 1 ], "name": "Junfeng Su" }, { "affs": [ 2 ], "name": "Yan Du" }, { "affs": [ 3 ], "name": "Chen Zhu" }, { "affs": [ 4 ], "name": "Haodong Zhou" }, { "affs": [ 5 ], "name": "Huyan Wang" }, { "affs": [ 6 ], "name": "Yinjun Du" }, { "affs": [ 7 ], "name": "Qiyuan Wang" }, { "affs": [ 8 ], "name": "Zexin Chen" }, { "affs": [ 9 ], "name": "Hanjun Cao" }, { "affs": [ 0, 1 ], "name": "Man Huang" }, { "affs": [ 2 ], "name": "Jing Xue" } ], "bibtex": "https://research.draconitic.com/paper/e60dhhdzkag7c.bib", "cited_by": 0, "doi": "10.3389/fimmu.2026.1960409", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719467/?tool=EBI", "id": "e60dhhdzkag7c", "issns": [ "1664-3224" ], "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960409/full", "language": "eng", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Research" ], [ "openalex", "2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis" ] ], "openalex": "W7222416628", "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1960409/pdf", "pmcid": "PMC13719467", "pmid": "42964222", "published": "2026-10-16", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/e60dhhdzkag7c.ris", "sources": [ { "first_seen": "2026-10-30T12:19:17Z", "native_id": "10.3389/fimmu.2026.1960409", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1960409/full" }, { "first_seen": "2026-10-31T12:21:36Z", "native_id": "PMC:PMC13719467", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13719467" }, { "first_seen": "2026-11-02T12:23:25Z", "native_id": "PMC13719467", "source": "pmc", "url": "https://doi.org/10.3389/fimmu.2026.1960409" } ], "subjects": [ { "field": "biology", "origin": "issn:1664-3224", "subfield": "immunology" } ], "title": "Anti-Ro52/TRIM21 seropositivity in interstitial lung disease: effect modification by disease subtype and myositis-specific antibody context", "title_text": "Anti-Ro52/TRIM21 seropositivity in interstitial lung disease: effect modification by disease subtype and myositis-specific antibody context", "type": "peer-reviewed", "updated_at": "2026-11-03T12:20:31Z", "url": "https://research.draconitic.com/paper/e60dhhdzkag7c", "venue": "Frontiers in Immunology", "versions": [] }