Distinct molecular and immunological properties of circulating exosomes isolated from pediatric lung transplant recipients with bronchiolitis obliterans syndrome - a retrospective study.
Transpl Int
; 33(11): 1491-1502, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-33448479
ABSTRACT
Long-term success following human lung transplantation is poor due to chronic rejection. We demonstrated circulating exosomes of lung origin during acute and chronic lung allograft rejection. We analyzed plasma from pediatric lung transplant recipients (LTxRs) enrolled in the CTOT-C-03 to determine whether circulating exosomes are released into circulation during bronchiolitis obliterans syndrome (BOS). Plasma exosomes were isolated, and human leukocyte antigens (HLA) were detected. Exosomes were analyzed for lung self-antigens (SAgs), co-stimulatory molecules transcription factors, major histocompatibility complex class II (MHC-II), adhesion molecules, and 20S proteasome. Mice were immunized with exosomes from BOS or stable to determine their immunogenicity. Circulating exosomes from BOS LTxRs contained increased levels of SAgs, donor HLA class I, MHC-II, transcription factors, co-stimulatory molecules, and 20S proteasome compared with stable. Serial analysis of exosomes containing SAgs demonstrated that exosomes are detectable in the circulation before BOS. Mice immunized with exosomes from BOS, or stable, demonstrated that exosomes from BOS are distinct in inducing both humoral and cellular immune responses to SAgs. Circulating exosomes from BOS LTxRs elicit distinct humoral and cellular response. In addition, detection of SAgs on circulatory exosomes 12 months before diagnosis of BOS suggest that exosomes could serve as biomarker.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Bronquiolitis Obliterante
/
Trasplante de Pulmón
/
Exosomas
Tipo de estudio:
Observational_studies
Límite:
Animals
/
Child
/
Humans
Idioma:
En
Revista:
Transpl Int
Asunto de la revista:
TRANSPLANTE
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos