Respiratory Viral Infections Following Human Lung Transplant Can Induce Exosomes with Lung Self-Antigens, Kα1Tubulin and Collagen V.
1Norton Thoracic Institute, St. Joseph's Hospital and Med Center, Phoenix
2Div Allergy &
Infectious Diseases, Univ Washington, Seattle
Meeting: 2017 American Transplant Congress
Abstract number: 156
Keywords: Autoimmunity
Session Information
Session Name: Concurrent Session: Lung Transplantation from Donation to Retransplantation
Session Type: Concurrent Session
Date: Sunday, April 30, 2017
Session Time: 4:30pm-6:00pm
Presentation Time: 5:18pm-5:30pm
Location: E270
Background: Respiratory viral infections (RVI) following human lung transplant (LTx) have been shown to increase the risk for development of chronic lung allograft dysfunction (CLAD). We demonstrated that lung transplant recipients (LTxR) diagnosed with acute and chronic rejection, but not stable, have circulating exosomes containing donor human leukocyte antigens (HLA) and lung associated self-antigens (SAgs). In this study we analyzed for the ability of RVI to induce exosomes containing lung SAgs to test the hypothesis that the released circulating exosomes, following viral infections, may play a role in the development of immune responses leading to CLAD.
Method: Sera was collected from LTxR diagnosed with RVI requiring treatment (n=10) and stable LTxR (n=5) done at the same time. Exosomes were isolated from serum by ultracentrifugation method and validated for the presence of exosome marker CD-9 and Alix. The presence of co-stimulatory molecules CD-80, CD-86 and donor HLA was determined using flow-cytometry. Lung SAgs, Kα1Tubulin (Kα1T) and Collagen V (Col-V), in the isolated exosomes, were performed using immunoblotting and densitometry.
Results: Exosomes isolated from RVI and stable LTxR demonstrated the presence of exosome marker CD-9 and Alix analyzed by immunoblot. However, only exosomes from RVI patients demonstrated significantly increased concentration of Col-V (mean optical density, RVI, 2.5±0.61 vs Stable 0.5±0.09, p=0.031) and Kα1T (RVI, 3.14±1.5 vs Stable 0.18±0.094, p=0.027). In addition, co-stimulatory molecules (CD-80, CD-86) and donor HLA was also demonstrable in exosomes isolated from RVI patients, but not in stable LTxR.
Conclusion: RVI following human LTx can induce exosomes containing lung SAgs, as well as donor HLA, indicating that the exosomes are originating from the transplanted organ. The exosomes expressed not only lung SAgs but also various costimulatory molecules and, therefore, will be immunogenic, increasing the risk for CLAD.
CITATION INFORMATION: Gunasekaran M, Limaye A, Sharma M, Biswas Roy S, Bansal S, Walia R, Bremner R, Smith M, Mohanakumar T. Respiratory Viral Infections Following Human Lung Transplant Can Induce Exosomes with Lung Self-Antigens, Kα1Tubulin and Collagen V. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Gunasekaran M, Limaye A, Sharma M, Roy SBiswas, Bansal S, Walia R, Bremner R, Smith M, Mohanakumar T. Respiratory Viral Infections Following Human Lung Transplant Can Induce Exosomes with Lung Self-Antigens, Kα1Tubulin and Collagen V. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/respiratory-viral-infections-following-human-lung-transplant-can-induce-exosomes-with-lung-self-antigens-k1tubulin-and-collagen-v/. Accessed May 25, 2025.« Back to 2017 American Transplant Congress