The Role of Immune Checkpoints in Lung Transplant (ILTRA)

Institute of Hospitalization and Scientific Care (IRCCS)

Status: Not yet enrolling

Conditions: Lung Transplant Rejection

Treatments: Diagnostic Test: Gene expression analysis; Diagnostic Test: Immune checkpoints analysis

Study type: Observational

Funder types: Other

Identifiers

NCT06302556

2022XJ9W4F

G53D2300526 0006 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment: 280 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Lung transplant patients

Exclusion criteria

• Hyperimmunized patients
• History of auto-immune disorders

Trial design

280 participants in 3 patient groups

Lung re-transplant cohort

Description:

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.

Treatment:

Diagnostic Test: Immune checkpoints analysis

Previous lung transplant cohort

Description:

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.

Treatment:

Diagnostic Test: Immune checkpoints analysis

Prospective lung transplant cohort

Description:

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.

Treatment:

Diagnostic Test: Immune checkpoints analysis

Diagnostic Test: Gene expression analysis