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Connective tissue diseases (CTDs) are an important secondary cause of interstitial lung disease (ILD). If a CTD is suspected, clinicians are recommended to perform autoantibody testing, including for myositis autoantibodies. In this study, the prevalence and clinical associations of novel myositis autoantibodies in ILD are presented. A total of 1194 patients with ILD and 116 healthy subjects were tested for antibodies specific for Ks, Ha, Zoα, and cN1A with a line-blot assay on serum available at the time of diagnosis. Autoantibodies were demonstrated in 63 (5.3%) patients and one (0.9%) healthy control ( p = 0.035). Autoantibodies were found more frequently in females ( p = 0.042) and patients without a histological and/or radiological usual interstitial pneumonia (UIP; p = 0.010) and a trend towards CTD-ILDs (8.4%) was seen compared with other ILDs (4.9%; p = 0.090). The prevalence of antibodies specific for Ks, Ha, Zoα, and cN1A was, respectively, 1.3%, 2.0%, 1.4%, and 0.9% in ILD. Anti-Ha and Anti-Ks were observed in males with unclassifiable idiopathic interstitial pneumonia (unclassifiable IIP), hypersensitivity pneumonitis (HP), and various CTD-ILDs, whereas anti-cN1A was seen in females with antisynthetase syndrome (ASS), HP, and idiopathic pulmonary fibrosis (IPF). Anti-Zoα was associated with CTD-ILD (OR 2.5; 95%CI 1.11-5.61; p = 0.027). In conclusion, a relatively high prevalence of previously unknown myositis autoantibodies was found in a large cohort of various ILDs. Our results contribute to the awareness that circulating autoantibodies can be found in ILDs with or without established CTD. Whether these antibodies have to be added to the standard set of autoantibodies analysed in conventional myositis blot assays for diagnostic purposes in clinical ILD care requires further study.

Prevalence of Novel Myositis Autoantibodies in a Large Cohort of Patients with Interstitial Lung Disease