Role for Club Cell Secretory Protein in Inducing Exosomes and Activation of Immune Responses in Lung Transplanted Recipients for Cystic Fibrosis
1St. Joseph’s Hospital and Medical Center, Phoenix, AZ, 2University of Texas Southwestern, Dallas, TX
Meeting: 2022 American Transplant Congress
Abstract number: 335
Keywords: Alloantibodies, Autoimmunity, Liver transplantation, Natural killer cells
Topic: Clinical Science » Lung » 64 - Lung: All Topics
Session Information
Session Name: Early and Late Outcomes in Lung Transplantation
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 6, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 5:50pm-6:00pm
Location: Hynes Room 210
*Purpose: Our lab has demonstrated that lower club cell secretory protein leads to immune responses to donor HLA and lung self-antigens (Collagen V, Kα1 Tubulin), and induction of exosomes with natural killer cell-associated molecules (NKp46, NKG2D). Studies have demonstrated cystic fibrosis (CF) patients after lung transplant (LTx) had significantly higher susceptibility to Pseudomonas infections suggesting deficiencies in innate immunity. Towards understanding the mechanisms, we analyzed the development of Abs to club cell secretory protein for contributing for the loss of club cell secretory protein leading to induction of exosomes with lung self-antigens, Pseudomonas aeruginosa, outer membrane porin F protein (oprF) and natural killer cell molecules.
*Methods: LTxs performed for CF and chronic obstructive pulmonary disease were included in this preliminary study (n=7). Club cell secretory protein levels in bronchoalveolar lavage and Abs to club cell secretory protein in plasma were determined by ELISA. oprF, natural killer cell molecules and lung self-antigens in circulating exosomes were determined by western blot.
*Results: The CF patients demonstrated significantly increased levels of pre-existing Abs to club cell secretory protein prior to LTx (p<0.05), post-LTx 3-6 month (p<0.05), and persisted at 1 year. CF LTx recipients (LTxRs) with Pseudomonas aeruginosa infection had bronchoalveolar lavage club cell secretory protein level significantly lower (p<0.05) than chronic obstructive pulmonary disease LTxRs. CF LTxRs also had a higher incidence of donor specific Ab (70%) compared to chronic obstructive pulmonary disease (22%) p<0.05.In addition, CF LTxRs had significantly higher levels of Abs to both lung self-antigens (p< 0.01) prior to LTx and Abs to Collagen V persisted after LTx at 1 year (p<0.05). Exosomes isolated from plasma at 6 months after LTx demonstrated increased levels of lung self-antigens (p<0.05), natural killer cell associated molecules NKG2D (p<0.01) and NKp46 (p<0.05), oprF (p<0.05) in CF LTxRs.
*Conclusions: We conclude that CF patients have pre-existing Abs to club cell secretory protein which continue to persist after LTx which may be responsible for the loss of club cell secretory protein in CF patients after LTx leading to exosome induction with natural killer cell molecules and oprF leading to immune response to donor MHC and lung self-antigens resulting in rejection.
To cite this abstract in AMA style:
Ravichandran R, Kaza V, Bremner R, Smith M, Mohanakumar T. Role for Club Cell Secretory Protein in Inducing Exosomes and Activation of Immune Responses in Lung Transplanted Recipients for Cystic Fibrosis [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/role-for-club-cell-secretory-protein-in-inducing-exosomes-and-activation-of-immune-responses-in-lung-transplanted-recipients-for-cystic-fibrosis/. Accessed May 18, 2025.« Back to 2022 American Transplant Congress