Quadruple-negative autoantibody status and interstitial lung disease progression in systemic sclerosis

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ID: 333756
2026
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Ranked #67 of 76 articles by views in Rheumatology Advances in Practice

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Abstract
Abstract Objectives To evaluate the association between disease-specific autoantibody profiles and disease progression in systemic sclerosis-associated interstitial lung disease (SSc-ILD), with a focus on a quadruple-negative phenotype. Methods This retrospective cohort study included 80 patients with SSc-ILD who were followed for at least 12 months at a single tertiary centre. ILD progression was defined according to the OMERACT criteria and/or worsening on high-resolution computed tomography. Autoantibody status was categorized based on four antibodies: anti-topoisomerase I, anti-centromere, anti-RNA polymerase III, and anti-U1-RNP. Quadruple-negative (QN) was defined as negativity for all four antibodies. Factors associated with ILD progression were evaluated using multivariable logistic regression. Exploratory comprehensive autoantibody profiling was performed in patients with available stored serum samples. Results During a median follow-up of 44.5 months, disease progression occurred in 32 of 80 patients with SSc-ILD. Anti-centromere antibody (ACA) positivity was associated with a lower risk of progression, whereas anti-topoisomerase I antibody positivity was not associated with disease progression (Model 2: OR 3.19, 95% CI 0.70–14.60). Compared with ACA positivity, QN status was associated with ILD progression (Model 2: OR 10.40, 95% confidence interval [CI] 1.77–60.70). However, CIs were wide. Exploratory analyses showed a high prevalence of anti-Ro-52 antibody positivity among patients with QN status. Conclusion QN autoantibody status may be associated with an increased risk of ILD progression in SSc. The QN status may represent a heterogeneous serological category that could help identify patients who require closer clinical monitoring. However, these results are hypothesis-generating and require validation in larger, independent cohorts.
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Authors Takeshi Kawaguchi, Kunihiko Umekita, Masayuki Murai, Chihiro Iwao, Masatoshi Kimura, Michikazu Nakai, Taiga Miyazaki
Journal Rheumatology Advances in Practice
Year 2026
DOI
10.1093/rap/rkag127
URL
https://doi.org/10.1093/rap/rkag127
Keywords Keywords not found

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