Date: Monday, June 3, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 5:30pm-5:42pm
Location: Room 206
*Purpose: Club cell secretory protein (CCSP) levels have been employed as a biomarker for respiratory stress in athletes, asthma patients, and in experimental acute and chronic lung injury models. A significant reduction in bronchoalveolar lavage fluids (BALF) CCSP levels and club cell numbers has been reported in lung transplant recipients (LTxRs) who develop bronchiolitis obliterans syndrome (BOS) compared to stable LTxRs. Goal of this study is to determine decline in CCSP and its correlation with induction of de novo development of Abs to lung-associated self-antigens (SAgs), Kα1 Tubulin (Kα1T) and Collagen V (Col-V), in LTxRs diagnosed with BOS.
*Methods: BALF from LTxRs diagnosed as having BOS (ISHLT criterion) were obtained for this study. CCSP levels in cell-free BALF were analyzed by ELISA (BioVendor, Asheville, NC). Development of Abs to lung SAgs, Kα1T- and ColV-, were determined by ELISA. Cytokines (i.e., G-CSF, GM-CSF, IFN-α, IFN-γ, IL-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17 and TNF-α), chemokines (i.e., Eotaxin, IP-10, MCP-1, MIG, MIP-1α, MIP-1β and RANTES), and growth factor levels (i.e., EGF, FGF-basic, HGF and VEGF) in BALF was analyzed by a 30-plex Luminex panel (ThermoFisher, Waltham, MA).
*Results: LTxRs with BOS (n=22) demonstrated significant decline in BALF CCSP level (58.6± 13.2 ng/ml) (p<0.05) as compared to stable patients (n=43) (65.6±11.9ng/ml). BOS (n=5) patients who developed Abs to lung SAgs had lower level of CCSP (58.6±12.2ng/ml) (p<0.05) in BALF as compared to CCSP levels (68.0±11.3ng/ml) of stable patient (n=25) who did not develop Abs to SAgs. LTxRs with BOS (n=7) who had lower levels of CCSP (43.2±12.3ng/ml) demonstrated increased levels of IL-6, IL-8, IL-1RA, IP-10, MCP-1, RANTES) levels though not statistically significant. However, BOS (n=7) LTxRs who had lower levels of CCSP (43.2±12.3ng/ml) also had significantly lower levels of VEGF (1.07±0.33pg/ml) as compared to stable (n=7) LTxRs (VEGF: 1.42±.58pg/ml) (p<0.05).
*Conclusions: We propose that a progressive decline in CCSP has a role in initiation of the cascade of inflammatory process and immune responses to lung SAgs, Col-V and Kα1T, which may contribute to the pathogenesis of chronic rejection following lung transplantation.
To cite this abstract in AMA style:Itabashi Y, Ravichandran R, Sharma M, Hachem R, Bremner R, Smith M, Mohanakumar T. Decline in Club Cell Secretory Protein Results in Immune Responses to Lung Self-Antigens (Kα1 Tubulin and Collagen V) and Development of Chronic Rejection Following Human Lung Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/decline-in-club-cell-secretory-protein-results-in-immune-responses-to-lung-self-antigens-k%ce%b11-tubulin-and-collagen-v-and-development-of-chronic-rejection-following-human-lung-transplantation/. Accessed May 9, 2021.
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