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Hum Immunol. 2018 Sep;79(9):653-658. doi: 10.1016/j.humimm.2018.06.005. Epub 2018 Jun 15.

Tissue-associated self-antigens containing exosomes: Role in allograft rejection.

Author information

1
Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
2
Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA. Electronic address: tm.kumar@dignityhealth.org.

Abstract

Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n = 30), heart (n = 8), or kidney (n = 15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot. Lung transplant recipients diagnosed with bronchiolitis obliterans syndrome had exosomes with higher expression of Col-V (4.2-fold) and Kα1T (37.1-fold) than stable. Exosomes isolated from heart transplant recipients diagnosed with coronary artery vasculopathy had a 3.9-fold increase in myosin and a 4.7-fold increase in vimentin compared with stable. Further, Kidney transplant recipients diagnosed with transplant glomerulopathy had circulating exosomes with a 2-fold increased expression of fibronectin and 2.5-fold increase in Col-IV compared with stable. We conclude that circulating exosomes with tissue associated SAgs have the potential to be a noninvasive biomarker for allograft rejection.

KEYWORDS:

Allograft rejection; Biomarker; Exosomes; Self-antigens; Tissue restricted antigens

PMID:
29908844
PMCID:
PMC6098724
[Available on 2019-09-01]
DOI:
10.1016/j.humimm.2018.06.005
[Indexed for MEDLINE]

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