Circulating exosomes with lung self-antigens as a biomarker for chronic lung allograft dysfunction: A retrospective analysis

Monal Sharma, Muthukumar Gunasekaran, Ranjithkumar Ravichandran, Cynthia E. Fisher, Ajit P. Limaye, Chengcheng Hu, John McDyer, Vaidehi Kaza, Ankit Bharat, Sofya Tokman, Ashraf Omar, Ashwini Arjuna, Rajat Walia, Ross M. Bremner, Michael A. Smith, Ramsey R. Hachem, Thalachallour Mohanakumar

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Exosomes isolated from plasma of lung transplant recipients (LTxRs) with bronchiolitis obliterans syndrome (BOS) contain human leukocyte antigens and lung self-antigens (SAgs), K-alpha 1 tubulin (Kα1T) and collagen type V (Col-V). The aim was to determine the use of circulating exosomes with lung SAgs as a biomarker for BOS. METHODS: Circulating exosomes were isolated retrospectively from plasma from LTxRs at diagnosis of BOS and at 6 and 12 months before the diagnosis (n = 41) and from stable time-matched controls (n = 30) at 2 transplant centers by ultracentrifugation. Exosomes were validated using Nanosight, and lung SAgs (Kα1T and Col-V) were detected by immunoblot and semiquantitated using ImageJ software. RESULTS: Circulating exosomes from BOS and stable LTxRs demonstrated 61- to 181-nm vesicles with markers Alix and CD9. Exosomes from LTxRs with BOS (n = 21) showed increased levels of lung SAgs compared with stable (n = 10). A validation study using 2 separate cohorts of LTxRs with BOS and stable time-matched controls from 2 centers also demonstrated significantly increased lung SAgs–containing exosomes at 6 and 12 months before BOS. CONCLUSIONS: Circulating exosomes isolated from LTxRs with BOS demonstrated increased levels of lung SAgs (Kα1T and Col-V) 12 months before the diagnosis (100% specificity and 90% sensitivity), indicating that circulating exosomes with lung SAgs can be used as a non-invasive biomarker for identifying LTxRs at risk for BOS.

Original languageEnglish (US)
JournalJournal of Heart and Lung Transplantation
DOIs
StateAccepted/In press - 2020

Keywords

  • biomarker
  • chronic lung allograft dysfunction
  • circulating exosomes
  • human lung transplant
  • lung self-antigens

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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  • Cite this

    Sharma, M., Gunasekaran, M., Ravichandran, R., Fisher, C. E., Limaye, A. P., Hu, C., McDyer, J., Kaza, V., Bharat, A., Tokman, S., Omar, A., Arjuna, A., Walia, R., Bremner, R. M., Smith, M. A., Hachem, R. R., & Mohanakumar, T. (Accepted/In press). Circulating exosomes with lung self-antigens as a biomarker for chronic lung allograft dysfunction: A retrospective analysis. Journal of Heart and Lung Transplantation. https://doi.org/10.1016/j.healun.2020.07.001