Diagnosis of myositis-associated interstitial lung disease: Utility of the myositis autoantibody line immunoassay

Adelle S Jee; Matthew J S Parker; Jane F Bleasel; Lauren K Troy; Edmund M Lau; Helen E Jo; Alan K Y Teoh; Susanne Webster; Stephen Adelstein; Tamera J Corte

doi:10.1016/j.rmed.2021.106581

Diagnosis of myositis-associated interstitial lung disease: Utility of the myositis autoantibody line immunoassay

Respir Med. 2021 Oct:187:106581. doi: 10.1016/j.rmed.2021.106581. Epub 2021 Aug 21.

Authors

Affiliations

¹ Department of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia; National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Pulmonary Fibrosis, Australia. Electronic address: adelle.jee@health.nsw.gov.au.
² Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia; National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Pulmonary Fibrosis, Australia; Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: matthew.parker@health.nsw.gov.au.
³ Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia; Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: jane.bleasel@sydney.edu.au.
⁴ Department of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia. Electronic address: ltroy@med.usyd.edu.au.
⁵ Department of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia. Electronic address: edmundmtlau@gmail.com.
⁶ Department of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia; National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Pulmonary Fibrosis, Australia. Electronic address: helen.jo@sydney.edu.au.
⁷ Department of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia; National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Pulmonary Fibrosis, Australia. Electronic address: alan_tky@yahoo.com.
⁸ Department of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia. Electronic address: susanne.webster@health.nsw.gov.au.
⁹ Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia; Central Immunology Laboratory, NSW Health Pathology, NSW, Australia; Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, NSW, Australia. Electronic address: stephen.adelstein@sydney.edu.au.
¹⁰ Department of Respiratory, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, NSW, Australia; National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Pulmonary Fibrosis, Australia. Electronic address: tameracorte@me.com.

PMID: 34454312
DOI: 10.1016/j.rmed.2021.106581

Abstract

Objectives: The detection of myositis autoantibodies (MA) in patients with interstitial lung disease (ILD) has major implications for diagnosis and management, especially amyopathic and forme frustes of idiopathic inflammatory myositis-associated ILD (IIM-ILD). Use of the MA line immunoblot assay (MA-LIA) in non-rheumatological cohorts remains unvalidated. We assessed the diagnostic performance of the MA-LIA and explored combined models with clinical variables to improve identification of patients with IIM-ILD.

Methods: Consecutive patients referred to a specialist ILD clinic, with ILD-diagnosis confirmed at multidisciplinary meeting, and MA-LIA performed within six months of baseline were included. Pre-specified MA-LIA thresholds were evaluated for IIM-ILD diagnosis.

Results: A total 247 ILD patients were included (IIM-ILD n = 12, non-IIM connective tissue disease-associated ILD [CTD-ILD] n = 52, idiopathic interstitial pneumonia [IIP] n = 115, other-ILD n = 68). Mean age was 64.8 years, with 45.3% female, mean FVC 75.5% and DLCO 59.2% predicted. MA were present in 13.8% overall and 83.3% of IIM-ILD patients. The most common MA in IIM-ILD and non-IIM ILD patients were anti-Jo-1 (prevalence 40%) and anti-PMScl (29.2%) autoantibodies respectively. The pre-specified low-positive threshold (>10 signal intensity) had the highest discriminative capacity for IIM-ILD (AUC 0.86). Combining MA-LIA with age, gender, clinical CTD-manifestations and an overlap non-specific interstitial pneumonia/organising pneumonia pattern on HRCT improved discrimination for IIM-ILD (AUC 0.96).

Conclusion: The MA-LIA is useful to support a diagnosis of IIM-ILD as a complement to multi-disciplinary ILD assessment. Clinical interpretation is optimised by consideration of the strength of the MA-LIA result together with clinical and radiological features of IIM-ILD.

Keywords: Autoimmune disease; Connective tissue disease; Immunoblot; Interstitial lung disease; Myositis autoantibody.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies, Antinuclear / blood*
Autoantibodies / blood*
Biomarkers / blood
Exosome Multienzyme Ribonuclease Complex / immunology
Female
Humans
Immunoassay / methods*
Lung Diseases, Interstitial / diagnosis*
Lung Diseases, Interstitial / etiology
Lung Diseases, Interstitial / immunology*
Male
Middle Aged
Myositis / complications
Myositis / diagnosis*
Myositis / immunology*
RNA-Binding Proteins / immunology

Substances

Antibodies, Antinuclear
Autoantibodies
Biomarkers
EXOSC9 protein, human
Jo-1 antibody
RNA-Binding Proteins
Exosome Multienzyme Ribonuclease Complex