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

JOURNAL OF HEART AND LUNG TRANSPLANTATION

卷:39

Article

Sharma, Monal¹  Gunasekaran, Muthukumar¹  Ravichandran, Ranjithkumar¹  Fisher, Cynthia E.²  Limaye, Ajit P.²  Hu, Chengcheng³  McDyer, John⁴  Kaza, Vaidehi⁵  Bharat, Ankit⁶  Tokman, Sofya¹  Omar, Ashraf¹  Arjuna, Ashwini¹  Walia, Rajat¹  Bremner, Ross M.¹  Smith, Michael A.¹  Hachem, Ramsey R.⁷  Mohanakumar, Thalachallour¹ 

[1] St Josephs Hosp, Norton Thorac Inst, 124 W Thomas Rd,Suite 105, Phoenix, AZ 85013 USA

[2] Univ Washington, Deparment Med, Seattle, WA 98195 USA

[3] Univ Arizona, Dept Epidemiol & Biostat, Phoenix, AZ USA

[4] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA

[5] Univ Texas Southwestern, Internal Med Pulm Dis, Dallas, TX USA

[6] Northwestern Univ, Dept Surg Thorac, Chicago, IL 60611 USA

[7] Washington Univ, Dept Internal Med, Med Sch, St Louis, MO 63110 USA

关键词: circulating exosomes;    biomarker;    lung self-antigens;    chronic lung allograft dysfunction;    human lung transplant;   

DOI  :  10.1016/j.healun.2020.07.001

来源: Elsevier

【 摘 要 】

BACKGROUND: Exosomes isolated from plasma of lung transplant recipients (LTxRs) with bronchioli-tis obliterans syndrome (BOS) contain human leukocyte antigens and lung self-antigens (SAgs), K-alpha 1 tubulin (K alpha 1T) 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 (K alpha 1T 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 (K alpha 1T 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. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

【 授权许可】

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