Signal or noise? Apply myositis autoantibody line-blot immunoassays in real-world settings: implications for...

Interpreting myositis autoantibody line-blot immunoassay (LIA) is challenging when balancing clinical relevance with autoantibody positivity strength. We evaluated its diagnostic values in real-world clinical practice.

A retrospective observational study of consecutive myositis LIA results in National Taiwan University Hospital from April 2021 to March 2023. We categorized the LIA testing indications into: suspected IIM, single clinical domain (pulmonary, muscular, joint, skin, and cardiovascular), and autoimmune work-ups. Individual autoantibody positive predictive value (PPV) for clinically diagnosed IIM was analyzed according to testing indications.

A total of 677 cases were included, 162 patients with IIM and 130 were LIA + IIM. LIA demonstrated an overall sensitivity of 80.2% and specificity of 66.4% in diagnosing IIM. Suspected IIM exhibited the highest PPV (95.9%) compared to single clinical domains or autoimmune work-ups. Autoantibody PPV was generally high in suspected IIM. Anti-aminoacyl-tRNA synthetase antibodies and anti-MDA5 exhibited higher PPV in pulmonary manifestations. Overall autoantibody PPV was low in joint, skin manifestations, and autoimmune work-ups. Pulmonary manifestation accounted for the majority of testing indications, yet few were found with IIM as the final diagnosis. Among those with LIA-seropositivity, 30.7% had autoimmune features, and 25% had other connective tissue diseases. Most anti-synthetase syndrome cases (86.7%) were in a single-domain manifestation.

The positive predictive value of myositis autoantibodies detected by LIA varies with testing indications and autoantibody profiles, rather than autoantibody positivity strength alone. LIA seropositive non-IIM reflect evolving diseases. Amid growing concerns about potential false positives and negatives in LIA, this study emphasizes integrating clinical context and longitudinal assessment when ordering and interpreting LIA in real-world practices. Key Points • The positive predictive value (PPV) of individual myositis autoantibodies for clinically diagnosed IIM varies substantially with the testing indications and autoantibody profiles, rather than autoantibody positivity strength alone. • Most (86.7%) patients with anti-synthetase syndrome had LIA tested for only one clinical domain initially. • Integrating clinical context before testing and throughout longitudinal assessment is essential for accurate interpretation of LIA results in broader clinical applications.