Quantification of autoantibodies using a luminescent profiling method in autoimmune interstitial lung disease

作者：Peter D. Burbelo, J.A. Huapaya, Zohreh Khavandgar, Margaret Beach, Iago Pinal‐Fernandez, Andrew L. Mammen, John A. Chiorini, Payam Noroozi Farhadi, Frederick W. Miller, Adam Schiffenbauer, Kakali Sarkar, Blake M. Warner, Lisa G. Rider · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1462242 · 被引用次数：9 · 研究领域：Inflammatory Myopathies and Dermatomyositis、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Systemic Sclerosis and Related Diseases

Autoantibodies are important for the diagnosis of autoimmune interstitial lung disease (ILD). Standard immunoassays have limitations, including their qualitative nature and/or a narrow dynamic range of detection, hindering the usefulness of autoantibodies as biomarkers of disease activity. Here, the luciferase immunoprecipitation system (LIPS) was evaluated for measuring myositis-specific and other lung-related autoantibodies in 25 subjects with idiopathic inflammatory myopathies (IIM), 26 with Sjögren's disease (SjD), and 10 healthy volunteers. LIPS detected a broad dynamic range of autoantibodies, to MDA5, Jo-1, PL12, KS, U1-70K, and Ro52, and matched seropositivity status with established immunoassays. Robust anti-MDA5 autoantibodies in four IIM-ILD patients had a median value of 1,134,000 LU (IQR 473,000-2,317,000), which was 500 times higher than in 21 seronegative IIM patients. Markedly elevated anti-Jo-1 autoantibodies in five IIM-ILD patients demonstrated a median value of 1,177,000 LU (IQR: 604,000-2,520,000), which was 1000-fold higher than in seronegative patients. Robust anti-Ro52 and other anti-tRNA-synthetase autoantibodies were detected in a subset of IIM-ILD subjects. In SjD, only anti-U1-70K and KS autoantibodies were identified in ILD patients with a prevalence of 30% and 20%, respectively. In longitudinal samples of five IIM-ILD patients, anti-Jo-1 autoantibody levels paralleled clinical improvement of lung function. LIPS can accurately quantify autoantibod...