Clinical spectrum of antisynthetase antibody positivity in a non-preselected general hospital population

Antisynthetase antibodies (ASAbs) are associated with significant muscle and lung disease and account for 25–30% of myositis-specific antibodies. Published cohorts are largely clinically preselected, introducing recruitment bias. We aimed to describe the clinical features and outcomes associated with ASAb positivity in a non-preselected general hospital population. We conducted a retrospective cohort study of patients with a positive ASAb detected by line blot immunoassay (EUROIMMUN, Lübeck, Germany) through Hunter New England Pathology Service between 2004 and 2023. Inclusion was based solely on ASAb positivity, irrespective of clinical diagnosis. Clinical data were extracted from electronic records and analysed descriptively and comparatively. Of 1,681 myositis LIAs performed, 197 patients with positive ASAbs comprised the cohort. Antisynthetase syndrome (ASyS) was diagnosed in 61.4% using Connors’ criteria and 18.3% using Solomon’s criteria; 34% met CLASS criteria for definite ASyS, demonstrating substantial diagnostic variability. Interstitial lung disease (ILD) was present in 32.5%, inflammatory arthritis in 27.4%, and myositis 25.9%. Anti-PL-12 positivity was associated with higher ILD frequency and lower mean FVC and DLco. NSIP was the most common ILD pattern overall. Borderline antibody results were still associated with myositis and ILD. Five-year mortality (11.7%) and malignancy prevalence (16.2%) were higher than the Australian population estimates. To our knowledge, this represents the largest single-centre cohort defined by ASAb positivity irrespective of clinical diagnosis. Prototypic ASyS features were present in a minority with marked discordance across criteria. These findings demonstrate phenotypic heterogeneity and support further investigation into ASAb pathogenicity and specificity. Not applicable. This study was a retrospective observational cohort study and was not a clinical trial.