*Purpose: We have shown that circulating exosome with lung self-antigens (SAgs) are detectable 1 year prior to chronic lung allograft dysfunction, independent of circulating antibodies. We have previously reported that donor-specific HLA antibodies or antibodies to kidney SAgs (collagen IV [Col IV], fibronectin [FN], and perlecan [PL]) were not associated with progression to chronic immune injury (CII) at 1 and 2 years. Since circulating exosomes may not be absorbed by the transplanted organ and appear prior to development of antibodies, we postulated that circulating exosomes with SAgs will predict progression to CII in kidney transplant recipients (KTxR).

*Methods: Exosomes were isolated from serum of KTxR with biopsy-proven progression to CII at 1 year post transplant (n=25) and compared to controls with no progression (n=25). Progression was defined as KTxR with no chronic changes on the 4 month protocol biopsy who then had ci>1, cg>0 at 1 year protocol biopsy. Sera were collected at 1year post-transplant and exosomes were isolated by total exosome isolation (Invitrogen) and 0.22 µm filtered to obtain pure exosomes. Exosomes were separated by gel electrophoresis and analyzed with antibodies to Col IV, FN, and PL and nuclear factor kappa B (NF-κB). ROC analysis was performed from Western blotting results.

*Results: Both groups were similar at baseline, except for race (table 1). KTxR with CII showed increased levels of exosomes containing Col IV (1.98-fold) (p=0.057), FN (1.9-fold) (p=0.02), PL (5.5-fold) (p=0.004), and NFκB (2.8-fold) (p=0.06) as compared with controls. ROC analysis demonstrated good predictive capability (figure 1), especially for PL with AUC=0.8 sensitivity 72%, specificity 84%.

*Conclusions: Circulating exosomes in KTxR with biopsy-proven progression to CII at 1 year post-transplant contained increased levels of SAgs and NF-κB. Sensitivity and specificity analysis demonstrated that increased levels of SAgs in circulating exosomes can serve as potential biomarkers in predicting progression to CII.

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