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  • Serum proteomic profiling of rheumatoid arthritis–interstitial lung disease with a comparison to idiopathic pulmonary fibrosis

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Serum proteomic profiling of rheumatoid arthritis–interstitial lung disease with a comparison to idiopathic pulmonary fibrosis
  1. Xiaoping Wu1,
  2. Yunju Jeong2,3,
  3. Sergio Poli de Frías4,
  4. Imaani Easthausen5,
  5. Katherine Hoffman5,
  6. Clara Oromendia5,
  7. Shahrad Taheri6,
  8. Anthony J Esposito2,7,
  9. Luisa Quesada Arias4,
  10. Ehab A Ayaub2,
  11. Rie Maurer8,
  12. Ritu R Gill9,
  13. Hiroto Hatabu3,10,
  14. Mizuki Nishino3,10,
  15. Michelle L Frits11,
  16. Christine K Iannaccone11,
  17. Michael E Weinblatt3,11,
  18. Nancy A Shadick3,11,
  19. Paul F Dellaripa3,11,
  20. Augustine M K Choi1,
  21. Edy Y Kim2,3,
  22. Ivan O Rosas12,
  23. Fernando J Martinez1,
  24. Tracy J Doyle2,3
  1. 1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, New York, USA
  2. 2 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3 Harvard Medical School, Boston, Massachusetts, USA
  4. 4 Department of Medicine, Mount Sinai Medical Center, Miami Beach, Florida, USA
  5. 5 Department of Population Health Science, Division of Biostatistics, Weill Cornell Medicine, New York, New York, USA
  6. 6 Department of Medicine, Weill Cornell Medicine–Qatar, Ar-Rayyan, Qatar
  7. 7 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  8. 8 Center for Clinical Investigation, Brigham and Women's Hospital, Boston, Massachusetts, USA
  9. 9 Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  10. 10 Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  11. 11 Department of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts, USA
  12. 12 Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, Texas, USA
  1. Correspondence to Dr Tracy J Doyle, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA 02115; tjdoyle{at}bwh.harvard.edu

Abstract

Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets.

  • Interstitial Fibrosis
  • Rheumatoid lung disease

https://doi.org/10.1136/thorax-2021-217822

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    Footnotes

    • XW and YJ contributed equally.

    • Contributors XW, TJD, FJM, AMKC and IOR contributed to the conception and design of the study. XW, TJD, YJ, EYK, RM, SPdF, CO, KH, and IE were involved in the analysis and interpretation of data. All authors participated in drafting the work or critically revising it and provided approval of the manuscript to be submitted for publication.

    • Funding This work was supported by the National Institutes of Health (grant numbers K23 HL119558 and R03 HL148484) and Stony Wold-Herbert Fund Fellowship Grant (no grant number applicable). The Brigham Rheumatoid Arthritis Sequential Study is funded by grants from Bristol-Myers Squibb, Amgen, Crescendo Bioscience and Sanofi/Regeneron. The authors would like to thank the Clinical Research and Proteomics Cores at Weill Cornell Medicine–Qatar, supported by the Biomedical Research Program funded by Qatar Foundation. The funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard University, Weill Cornell Medicine, their affiliated academic healthcare centers or the National Institutes of Health.

    • Competing interests The authors have reported the following conflicts of interest, all outside the submitted work: ST reports medical advisory group membership of Novo Nordisk and board membership at Droobi Health, Qatar. RG receives grant support from Canon Medical Systems. HH reports grants from Canon Medical Systems and Konica Minolta, and personal fees from Mitsubishi Chemical Co and Canon Medical Systems Inc. MN reports grants from AstraZeneca, Daiichi Sankyo, Canon Medical Systems, Merck investigator studies program; personal fees from Daiichi Sankyo and AstraZeneca. MEW receives research support from Amgen, Bristol Myers Squibb and Eli Lilly and consultation fees from AbbVie, Aclaris, Amgen, Arena, Bayer, Bristol Myers Squibb, Corvitas, Eqrx, Genosco, GSK, Gilead, Horizon, Johnson & Johnson, Kiniksa, Lilly, Novartis, Pfizer, Rami Therapeutics, R Pharma, Roche, Sanofi, Scipher, Sci Rhom, Set Point and Tremeau. He holds stock/stock options of CanFite, Inmedix, Vorso and Scipher. NAS reports grants and other support from Bristol-Myers Squibb, grants from Mallinckrodt, Sanofi, Crescendo Biosciences, Lilly and Amgen. PFD reports grants from Bristol-Myers Squibb and Genentech, and other support from Boehringer Ingelheim. AMKC is a cofounder and equity stock holder for Proterris, which develops therapeutic uses for carbon monoxide, and also has a use patent on CO and a patent in chronic obstructive pulmonary disease. EYK is a member of the steering committees for and receives no financial remuneration from NCT04409834 (Prevention of arteriovenous thrombotic events in critically ill COVID-19 patients, TIMI group) and REMAP-CAP ACE2 renin–angiotensin system modulation domain, and receives unrelated research funding from Bayer AG, Roche Pharma Research and Early Development, Windtree Therapeutics, the US National Institutes of Health, the US Agency for International Development, the American Heart Association, American Lung Association and the Bell Family Fund. IOR reports grants from Genentech. FJM reports personal fees, non-financial support and other support from AstraZeneca, other support from Afferent/Merck, personal fees, non-financial support and other support from Boehringer Ingelheim, other support from Bristol Myers Squibb, other support from Chiesi, personal fees and non-financial support from the Canadian Respiratory Society, personal fees and non-financial support from CME Outfitters, personal fees and non-financial support from CSL Behring, personal fees from Dartmouth University, personal fees from France Foundation, personal fees from Gala, personal fees and non-financial support from Genentech, grants, personal fees, non-financial support and other support from GlaxoSmithKline, personal fees and non-financial support from Inova Fairfax, personal fees and non-financial support from MD Magazine, personal fees and non-financial support from NYP Methodist Hospital Brooklyn, personal fees and non-financial support from Miller Communications, personal fees and non-financial support from National Association for Continuing Education/Integritas, other support from Nitto, personal fees and non-financial support from Novartis, personal fees from New York University, personal fees and non-financial support from Patara/Respivant, personal fees from Pearl, personal fees and non-financial support from Peer View, personal fees from Physicians Education Resource, personal fees from ProMedior, personal fees and non-financial support from Rare Diseases Healthcare Communications, personal fees from Rockpointe Communications, personal fees and non-financial support from Sanofi/Regeneron, other support from Biogen, personal fees and non-financial support from Sunovion, personal fees and non-financial support from Teva, other support from two XAR, personal fees from University of Birmingham Alabama, personal fees from UpToDate, non-financial support from Veracyte, personal fees from Vindico, personal fees and non-financial support from WebMD/MedScape, non-financial support and other support from Zambon, non-financial support from ProTerrix Bio, and personal fees from IQVIA, Raziel, Abvie and Verona. TJD has received grant support from Bristol Myers Squibb, consulting fees from Boehringer Ingelheim and L.E.K. consulting, and has been part of a clinical trial funded by Genentech. The remaining authors have reported no conflicts of interest.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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