Key result
Circulating exosomes in pediatric lung transplant BOS show increased self-antigens and elicit distinct immune responses.
Why the study?
Long-term success after lung transplantation is limited by chronic rejection, prompting investigation into whether circulating exosomes are released into circulation during bronchiolitis obliterans syndrome.
Are circulating exosomes distinct in molecular and immunological properties in pediatric lung transplant recipients with bronchiolitis obliterans syndrome compared to stable recipients?
Cohort
Are circulating exosomes distinct in molecular and immunological properties in pediatric lung transplant recipients with bronchiolitis obliterans syndrome compared to stable recipients?
Circulating exosomes containing lung self-antigens are detectable up to 12 months before BOS diagnosis in pediatric lung transplant recipients, suggesting their potential as an early biomarker for chronic rejection.
Exosome profiling may enable earlier BOS detection in pediatric lung recipients; leaves open whether it can guide preventive interventions.
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.
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Sharma et al. (2020) conducted a cohort in Bronchiolitis obliterans syndrome in pediatric lung transplant recipients. Bronchiolitis obliterans syndrome (BOS) vs. Stable condition was evaluated on Exosomal levels of self-antigens, HLA, MHC-II, and immunogenicity. Circulating exosomes from pediatric lung transplant recipients with BOS contained increased levels of self-antigens and elicited distinct immune responses compared to stable patients.
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