The Role of Immune Checkpoints in Lung Transplant (ILTRA)
- Conditions
- Lung Transplant Rejection
- Interventions
- Diagnostic Test: Immune checkpoints analysisDiagnostic Test: Gene expression analysis
- Registration Number
- NCT06302556
- Brief Summary
The goal of this observational study is to learn about rejection in lung transplantation.
The main question it aims to answer is:
• what is the role of immune checkpoints in lung transplantation? Participants will describe pathways of rejection in lung transplantation analyzing the immune checkpoints on explanted lungs as well as trans-bronchial biopsies.
- Detailed Description
Lung transplantation is the less common solid organ transplant performed; it is the treatment of choice for end stage lung disease. Lung transplantation is "problematic" for a number of reasons: low graft availability, high waitlist mortality and unsatisfactory survival. Acute rejection, occurring days to months after surgery, has been identified as one of the main risk factors for the development of chronic rejection: in the first five years after lung transplantation, chronic rejection is the major cause of graft failure, morbidity and mortality. A deep knowledge of the immunological scenarios associated with lung graft tolerance could allow selectively switch-off T-cells involved in the rejection process. The researches, preliminary demonstrated the central role of immunological checkpoints in the development of acute rejection and its evolution towards chronic rejection. The aim of this study is the identification of markers that could be associated with the establishment of lung graft tolerance.
The project is articulated into two parts: a retrospective and a prospective section. The retrospective section is constituted by a cross-sectional study of immune checkpoints on lungs explanted during lung re-transplantation for chronic rejection (cohort 1). In addition, the retrospective section includes a retrospective cohort study of immune checkpoints on specimens from transbronchial lung biopsies of participants who received lung transplantation and have 3 years of follow-up (cohort 2). The prospective section is a cohort study of immune checkpoints on specimens from transbronchial lung biopsies and gene expression analysis on immune cells purified from bronchoalveolar lavage; participants will be subjects receiving the lung transplantation during the first year of recruitment and followed for one year (cohort 3).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 280
- Lung transplant patients
- Hyperimmunized patients
- History of auto-immune disorders
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Lung re-transplant cohort Immune checkpoints analysis This cohort includes consecutive participants who underwent lung re-transplantation for chronic lung allograft dysfunction from 2010 to 2020; the immune checkpoints analyses will be conducted on stored specimens from lungs explanted during re-transplantation. Previous lung transplant cohort Immune checkpoints analysis This cohort includes participants who received first bilateral lung transplantation from 2017 to 2020. The immune checkpoints analyses will be conducted on stored specimens from postoperative transbronchial biopsy performed for clinical suspicious of rejection. Prospective lung transplant cohort Immune checkpoints analysis This cohort includes participants who will have their first bilateral lung transplant from April 2024 to April 2025. Immunopathological characterization of bronchoalveolar leukocytes and analysis of immuno checkpoints will be performed on leftover material of bronchoalveolar lavage and transbronchial lung biopsy samples performed for clinical suspicious of rejection. Prospective lung transplant cohort Gene expression analysis This cohort includes participants who will have their first bilateral lung transplant from April 2024 to April 2025. Immunopathological characterization of bronchoalveolar leukocytes and analysis of immuno checkpoints will be performed on leftover material of bronchoalveolar lavage and transbronchial lung biopsy samples performed for clinical suspicious of rejection.
- Primary Outcome Measures
Name Time Method Lung-tissue immune-checkpoint profile and bronchoalveolar immune-cells mRNA signature in acute rejection after lung transplantation. Twelve months after lung transplantation (prospective data) Prevalence of immune checkpoint markers and gene-expression on leukocytes from transbronchial biopsies and bronchoalveolar lavage. Participants: cohort number 3.
Lung-tissue immune-checkpoint profile in chronic rejection after lung transplantation. Cohort 1: at re-transplantation for chronic lung allograft dysfunction (cross-sectional data). Cohort 2: from one to 36 months after lung transplantation (retrospective data) Prevalence of immune checkpoint markers on leukocytes from explanted lung grafts and transbronchial biopsies. Participants: cohort number 1 and 2.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (4)
Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
University of Modena and Reggio Emilia
🇮🇹Modena, Italy
University of Padua
🇮🇹Padova, Italy
University of Turin
🇮🇹Torino, Italy