Myositis-specific Antibodies Identify A Distinct Interstitial Pneumonia with Autoimmune Features Phenotype

Julia Graham; Iazsmin Bauer Ventura; Chad A Newton; Cathryn Lee; Noelle Boctor; Janelle Vu Pugashetti; Claire Cutting; Elena Joerns; Habrinder Sandhu; Jonathan H Chung; Christine Kim Garcia; Michael Kadoch; Imre Noth; Ayodeji Adegunsoye; Mary E Strek; Justin M Oldham

doi:10.1183/13993003.01205-2020

Myositis-specific Antibodies Identify A Distinct Interstitial Pneumonia with Autoimmune Features Phenotype

Eur Respir J. 2020 Jul 16:2001205. doi: 10.1183/13993003.01205-2020. Online ahead of print.

Authors

Julia Graham^{1

2}, Iazsmin Bauer Ventura^{3

2}, Chad A Newton^{4

2}, Cathryn Lee⁵, Noelle Boctor¹, Janelle Vu Pugashetti⁶, Claire Cutting¹, Elena Joerns⁷, Habrinder Sandhu⁸, Jonathan H Chung⁹, Christine Kim Garcia¹⁰, Michael Kadoch¹¹, Imre Noth¹², Ayodeji Adegunsoye⁵, Mary E Strek^{5

2}, Justin M Oldham^{13

2}

Affiliations

¹ Department of Internal Medicine, University of California at Davis.
² These authors contributed equally.
³ Department of Medicine, Section of Rheumatology, University of Chicago.
⁴ Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern.
⁵ Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago.
⁶ Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Davis.
⁷ Department of Internal Medicine, Division of Rheumatology, University of Texas Southwestern.
⁸ Department of Internal Medicine, Division of Rheumatology, University of California at Davis.
⁹ Department of Radiology, The University of Chicago.
¹⁰ Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University.
¹¹ Department of Radiology, University of California at Davis.
¹² Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Virginia.
¹³ Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Davis joldham@ucdavis.edu.

Abstract

Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an anti-synthetase syndrome. Whether MSAs and myositis associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear.A multi-center, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis (IPF) and non-IIM CTD-ILDs. The primary endpoint assessed was three-year transplant-free survival. Two hundred sixty-nine patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.

Abstract

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