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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1462242
This article is part of the Research Topic Novel Biomarkers for Early Diagnosis, involved in Autoimmune and Autoinflammatory Diseases View all articles

Quantification of Autoantibodies Using a Luminescent Profiling Method in Autoimmune Interstitial Lung Diseases

Provisionally accepted
Peter Burbelo Peter Burbelo 1*Julio A. Huapaya Julio A. Huapaya 2*Zohreh Khavandgar Zohreh Khavandgar 3Margaret Beach Margaret Beach 3Iago Pinal-Fernandez Iago Pinal-Fernandez 4Andrew L. Mammen Andrew L. Mammen 4John Chiorini John Chiorini 1Payam Noroozi Farhadi Payam Noroozi Farhadi 5Frederick Miller Frederick Miller 5Adam Schiffenbauer Adam Schiffenbauer 5Kakali Sarkar Kakali Sarkar 5Blake M. Warner Blake M. Warner 6Lisa G. Rider Lisa G. Rider 5
  • 1 Adeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research (NIH), Bethesda, Illinois, United States
  • 2 Clinical Center (NIH), Bethesda, Maryland, United States
  • 3 National Institute of Dental and Craniofacial Research (NIH), Bethesda, Maryland, United States
  • 4 Muscle Disease Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH), Bethesda, Maryland, United States
  • 5 Clinical Research Branch, Division of Intramural Research, National Institute of Environmental Health Sciences (NIH), Durham, North Carolina, United States
  • 6 Epithelial and Salivary Gland Biology and Dysfunction, National Institute of Dental and Craniofacial Research (NIH), Bethesda, Maryland, United States

The final, formatted version of the article will be published soon.

    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 autoantibody levels as biomarkers for treatment response in patients with autoimmune ILD.

    Keywords: Interstitial lung disease, myositis-specific autoantibody, myositis-associated autoantibody, idiopathic inflammatory myopathies, Sjögren's disease Abbreviations: Creatine kinase, CK, DLCO, diffusing capacity of the lungs for carbon monoxide, FVC, forced vital capacity percent, ILD, interstitial lung diseases, IIM, idiopathic inflammatory myopathies, IQR, interquartile range, SjD, Sjogren's disease, LIPS

    Received: 09 Jul 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Burbelo, Huapaya, Khavandgar, Beach, Pinal-Fernandez, Mammen, Chiorini, Noroozi Farhadi, Miller, Schiffenbauer, Sarkar, Warner and Rider. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Peter Burbelo, Adeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research (NIH), Bethesda, 20894, Illinois, United States
    Julio A. Huapaya, Clinical Center (NIH), Bethesda, 20892, Maryland, United States

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