Ann Transplant Res | Volume 3, Issue 1 | Research Article | Open Access
Weigt SS1*, Chang LC1, Lari S1, Palchevskiy V1, Xue YY1, Shino MY1, Saggar R1, Sayah D1, Derhovanessian A1, Lynch JP III1, Ardehali A3, Belperio JA1
1Department of Medicine, David Geffen School of Medicine, University of California, USA 2Department of Medicine and Women’s Guild Lung Institute, Cedars-Sinai Medical Center, USA 3Department of Surgery, David Geffen School of Medicine, University of California, USA
*Correspondance to: S Samuel Weigt
Fulltext PDFBackground: Chronic Lung Allograft Dysfunction (CLAD) is the major limitation to long-term
survival following lung transplantation and the pathogenesis is thought to involve dysregulated
immune responses to various lung injuries. Type 1, Type 2, and Type 17 immune responses have
all been implicated.
Objective: Determine the relationship between immune response markers measured in
Bronchoalveolar Lavage (BAL) fluid and the development of CLAD.
Methods: We measured BAL concentrations by bead-based multiplex or ELISA for Type 1 (IL-
12p70, IFN-γ, CXCL9, CXCL10, CXCL11, CCL5), Type 2 (IL-4, IL-13, CCL2, CCL11), and Type
17 (IL-17, IL-6, TGF-β and CCL20) markers. For each marker, the estimated concentration at 6
months and composite variables for Type 1, Type 2, and Type 17 markers were generated using
Principal Component (PC) analysis. We used cumulative incidence competing risk regression to
determine associations with CLAD and death unrelated to CLAD.
Results: 57 lung transplant recipients had BAL samples before and after 6 months post-transplant;
19 never developed CLAD and 38 developed CLAD. Type 1 (1st PC) and Type 2 (1st PC) immune
response markers were associated with CLAD development. In addition, Type 1 (2nd PC) and Type
17 (2nd PC) immune response markers were associated with death unrelated to CLAD.
Conclusion: We demonstrate that alterations in Type 1, Type 2, and Type 17 immune responses
precede CLAD and mortality in lung transplant recipients. Larger longitudinal studies to assess
prognostic utility are warranted.
Lung transplantation; Chronic lung allograft dysfunction; Immune response
Weigt SS, Chang LC, Lari S, Palchevskiy V, Xue YY, Shino MY, et al. Immune Responses in the Lung Preceding a Diagnosis of Chronic Lung Allograft Dysfunction. Ann Transplant Res. 2023; 3(1): 1017..