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Autoantibodies are present in the bronchoalveolar lavage but not circulation in patients with fibrotic interstitial lung disease

Karim Boustani, Poonam Ghai, Rachele Invernizzi, Richard J. Hewitt, Toby M. Maher, Quan-Zhen Li, Philip L. Molyneaux, James A. Harker
ERJ Open Research 2021; DOI: 10.1183/23120541.00481-2021
Karim Boustani
1National Heart and Lung Institute, Imperial College London, London, UK
2Asthma UK Centre in Allergic Mechanisms of Asthma
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Poonam Ghai
1National Heart and Lung Institute, Imperial College London, London, UK
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Rachele Invernizzi
1National Heart and Lung Institute, Imperial College London, London, UK
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  • ORCID record for Rachele Invernizzi
Richard J. Hewitt
1National Heart and Lung Institute, Imperial College London, London, UK
3Royal Brompton Hospital, UK
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Toby M. Maher
1National Heart and Lung Institute, Imperial College London, London, UK
3Royal Brompton Hospital, UK
4Hastings Centre for Pulmonary Research and Division of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA
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Quan-Zhen Li
5Department of Immunology & Internal Medicine, Microarray and Immune Phenotyping Core Facility, University of Texas Southwestern Medical Centre, USA
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Philip L. Molyneaux
1National Heart and Lung Institute, Imperial College London, London, UK
3Royal Brompton Hospital, UK
6Denotes equal contribution
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James A. Harker
1National Heart and Lung Institute, Imperial College London, London, UK
2Asthma UK Centre in Allergic Mechanisms of Asthma
6Denotes equal contribution
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  • For correspondence: j.harker@imperial.ac.uk
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Abstract

Background Fibrotic interstitial lung disease (fILD) has previously been associated with the presence of autoantibody. While studies have focused on systemic autoimmunity, the role of local autoantibodies in the airways remains unknown. We therefore extensively characterised the airway and peripheral autoantibody profiles in patients with fILD and assessed association with disease severity and outcome.

Methods Bronchoalveolar lavage (BAL) was collected from a cohort of fILD patients and total BAL antibody concentrations were quantified. An autoantigen microarray was used to measure IgG and IgA autoantibodies against 122 autoantigens in BAL from 40 idiopathic pulmonary fibrosis (IPF), 20 chronic hypersensitivity pneumonitis (CHP), 20 connective tissue disease-associated ILD (CTD-ILD) patients and 20 controls.

Results A subset of patients with fILD but not healthy controls had a local autoimmune signature in their BAL that was not present systemically, regardless of disease. The proportion of patients with IPF with a local autoantibody signature was comparable to that of CTD-ILD, which has a known autoimmune pathology, identifying a potentially novel subset of patients. The presence of an airway autoimmune signature was not associated with reduced survival probability or changes in lung function in the cohort as a whole. Patients with IPF had increased BAL total IgA and IgG1 while subjects with CHP had increased BAL IgA, IgG1 and IgG4. In patients with CHP, increased BAL total IgA was associated with reduced survival probability.

Conclusion Airway autoantibodies that aren't present systemically identify a group of patients with fILD and the mechanisms by which these autoantibodies contribute to disease requires further investigation.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Karim Boustani has nothing to disclose.

Conflict of interest: Poonam Ghai has nothing to disclose.

Conflict of interest: Rachele Invernizzi has nothing to disclose.

Conflict of interest: Richard J. Hewitt has nothing to disclose.

Conflict of interest: Toby Maher reports grants and personal fees from GSK, personal fees from Boehringer Ingelheim, grants and personal fees from Astra Zeneca, personal fees from Roche, personal fees from Galapagos, personal fees from Celgene, personal fees from Pliant, personal fees from Blade Therapeutics, personal fees from Respivant, personal fees from Bristol-Myers Squibb, personal fees from Galecto, personal fees from Theravance, personal fees from IQVIA, personal fees from Veracyte, outside the submitted work.

Conflict of interest: Quan-Zhen Li has nothing to disclose.

Conflict of interest: Philip Molyneaux reports receiving grant funding to institution from AstraZeneca, outside the submitted work. Consulting speaker fees from Boehringer Ingelheim and Hoffman-La Roche, outside the submitted work.

Conflict of interest: James A. Harker has nothing to disclose.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received July 27, 2021.
  • Accepted October 23, 2021.
  • Copyright ©The authors 2021
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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Autoantibodies are present in the bronchoalveolar lavage but not circulation in patients with fibrotic interstitial lung disease
Karim Boustani, Poonam Ghai, Rachele Invernizzi, Richard J. Hewitt, Toby M. Maher, Quan-Zhen Li, Philip L. Molyneaux, James A. Harker
ERJ Open Research Jan 2021, 00481-2021; DOI: 10.1183/23120541.00481-2021

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Autoantibodies are present in the bronchoalveolar lavage but not circulation in patients with fibrotic interstitial lung disease
Karim Boustani, Poonam Ghai, Rachele Invernizzi, Richard J. Hewitt, Toby M. Maher, Quan-Zhen Li, Philip L. Molyneaux, James A. Harker
ERJ Open Research Jan 2021, 00481-2021; DOI: 10.1183/23120541.00481-2021
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