What question did this study set out to answer?

This research aims to understand how different subtypes of anti-ARS antibodies relate to the severity of interstitial lung disease.

May 20, 2026

D23-23 Association of Anti-aminoacyl-tRNA Synthetase (Anti-ARS) Antibody Subtypes With Severity and Evolution of Interstitial Lung Disease (ILD): An Analysis of the Class Project Database

Key Points

This research aims to understand how different subtypes of anti-ARS antibodies relate to the severity of interstitial lung disease.
Analyzed CLASS Project database of ASyS-ILD patients from 103 centers across 30 countries.
Excluded records with no anti-ARS results or multiple anti-ARS antibodies.
Employed linear and logistic regression to assess ILD severity and pulmonary function test outcomes.
Non-Jo-1 subtypes showed worse baseline pulmonary function tests (FVC 67% vs 73%, p = 0.032; DLCO 52% vs 60%, p < 0.001).
At follow-up, non-Jo-1 patients had lower FVC (77% vs 81%) and DLCO (56% vs 64%).
Anti-PL-7 was associated with increased risk of severe ILD on follow-up HRCT (adjusted OR 2.77).

Abstract

Abstract Background Antisynthetase syndrome (ASyS) is characterized by the presence of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies and a heterogeneous spectrum of clinical features, including interstitial lung disease (ILD), a major contributor to morbidity and mortality. ILD outcomes differ by anti-ARS subtype; non-Jo-1 is associated with a higher risk of progressive pulmonary fibrosis (PPF) and worse lung outcomes. We compared ILD severity in anti-Jo-1-positive versus non-anti-Jo-1-positive patients using large international data. Methods We analyzed the CLASS Project database, including adults with ASyS-ILD from 103 centers across 30 countries. Records without anti-ARS result or with 1 anti-ARS antibody were excluded. We compared anti-Jo-1 positive ILD patients vs non-Jo-1 subtypes (PL-7, PL-12, EJ, OJ, KS, Zo, and YRS/Ha). Lung variables included baseline and last PFTs (FVC% predicted, DLCO% predicted), HRCT pattern/severity, and ILD status at last follow-up. We performed linear regression for the last FVC% and DLCO%, and logistic regression to assess the association with severe ILD on follow-up HRCT. Multivariable models were adjusted for age, sex, smoking status, ethnicity, baseline pulmonary function, baseline HRCT pattern, diagnostic delay, and treatment; β coefficients and adjusted odds ratios with 95% CIs were reported (α = 0.05). Results Among 1,729 ASyS patients, 1,547 (89.5%) had ILD. Anti-Jo-1 was the most frequent subtype (61.8%); non-Jo-1 subtypes were PL-7 (12.8%), PL-12 (14.8%), EJ (6.5%), OJ (2.7%), KS (1.2%), and Zo (0.2%). Non-jo-1 patients had worse baseline PFTs (FVC 67% IQR 53-82 vs 73% 59-88, p = 0.032; DLCO 52% 40-65 vs 60% 47-72, p 0.001), with NSIP predominating and UIP 10%. At last follow-up (FVC n = 564; DLCO n = 524), non-Jo-1 remained lower (FVC 77% 59-91 vs 81% 67-98; DLCO 56% 41-71 vs 64% 48-78). In multivariable models, anti-PL-7 was associated with lower last DLCO and with severe ILD on follow-up HRCT (adjusted OR 2.77); baseline UIP also predicted severity (adjusted OR 2.78). Conclusion Non-Jo-1, especially anti-PL-7, was associated with more severe ILD, lower follow-up DLCO, and greater HRCT severity on follow-up. These findings support antibody-based risk stratification and closer pulmonary monitoring in this subgroup. This abstract is funded by: None

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