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Donor‐Derived Exosomes With Lung Self‐Antigens in Human Lung Allograft Rejection
Author(s) -
Gunasekaran M.,
Xu Z.,
Nayak D. K.,
Sharma M.,
Hachem R.,
Walia R.,
Bremner R. M.,
Smith M. A.,
Mohanakumar T.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13915
Subject(s) - microvesicles , bronchiolitis obliterans , immunology , alloimmunity , medicine , lung transplantation , lung , bronchoalveolar lavage , transplantation , immune system , human leukocyte antigen , cd63 , flow cytometry , antigen , microrna , biology , gene , surgery , biochemistry
The immunological role of exosomes in allograft rejection remains unknown. We sought to determine whether exosomes are induced during lung allograft rejection and to define the antigenic compositions of HLA , lung‐associated self‐antigens ( SA gs) and micro RNA s (mi RNA s). Exosomes were isolated from sera and bronchoalveolar lavage fluid from 30 lung transplant recipients ( LTxRs ) who were stable or who had acute rejection ( AR ) or bronchiolitis obliterans syndrome ( BOS ). Exosomes were defined by flow cytometry for CD 63 and western blotting for annexin V SA gs, collagen V (Col‐V) and Kα1 tubulin were examined by electron microscopy; mi RNA s were profiled by a mi RNA array. Donor HLA and SA gs were detected on exosomes from LTxR s with AR and BOS but not from stable LTxR s. Exosomes expressing Col‐V were isolated from sera from LTxR s 3 mo before AR and 6 mo before BOS diagnosis, suggesting that exosomes with SA gs may be a noninvasive rejection biomarker. Exosomes isolated from LTxR s with AR or BOS also contained immunoregulatory mi RNA s. We concluded that exosomes expressing donor HLA , SA gs and immunoregulatory mi RNA s are present in the circulation and local site after human lung transplantation and play an important role in the immune pathogenesis of acute allograft rejection and BOS .