The Role of Immune Checkpoints in Lung Transplant (ILTRA)

NCT06302556 | Not Yet Recruiting

• 2 other identifiers: 2022XJ9W4FG53D2300526 0006
• Study Type: observational
• Target: 280
• Locations: 1 country
• Sites: 4

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.

Conditions

Lung Transplant Rejection

Keywords

Lung transplantation; Immune checkpoint; Acute rejection; Chronic rejection; Chronic lung allograft dysfunction

Outcome Measures

Primary Outcomes (2)

• Lung-tissue immune-checkpoint profile and bronchoalveolar immune-cells mRNA signature in acute rejection after lung transplantation.

  Prevalence of immune checkpoint markers and gene-expression on leukocytes from transbronchial biopsies and bronchoalveolar lavage. Participants: cohort number 3.

  Twelve months after lung transplantation (prospective data)

• Lung-tissue immune-checkpoint profile in chronic rejection after lung transplantation.

  Prevalence of immune checkpoint markers on leukocytes from explanted lung grafts and transbronchial biopsies. Participants: cohort number 1 and 2.

  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)

Study Arms (3)

Lung re-transplant cohort

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.

Diagnostic Test: Immune checkpoints analysis

Previous lung transplant cohort

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.

Diagnostic Test: Immune checkpoints analysis

Prospective lung transplant cohort

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.

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

Interventions

Immune checkpoints analysis DIAGNOSTIC_TEST

The researcher will analyze immune checkpoint molecules, which will include the lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), V-domain Ig suppressor of T cell activation (VISTA), besides the canonical PD1 and ligands L1 and L2, T cell immunoglobulin and ITIM domain (TIGIT) and CTLA-4. In addition, Foxp3, GATA3 and TOX will be analyzed as specific lineage markers.

Lung re-transplant cohort; Previous lung transplant cohort; Prospective lung transplant cohort

Gene expression analysis DIAGNOSTIC_TEST

Immune cells will be purified from bronchoalveolar lavage; total RNA will be purified and subjected to gene expression analysis by Quantigene multiplex 80-plex Assay, which allows to evaluate simultaneously the follow mRNA targets: CCL2, CCL3, CCL5, CXCL10, CSF2, CSF3, IL1A, IL1B, IL1RN, IL6, IL6R, IL8, IL10, IL12B, IL17A, IL18, IL22, IL28A, TNF, TNFRSF4, IFNA2, IFNB1, IFNG, IFI16, IFITM1, IFITM3, MX1, TLR3, TLR4, TLR7, TLR8, NOD1, NOD2, CASP1, NLRP3, PYCARD, CD44, CLEC4M, CD209, ITGA4, ITGB7, CH25H, ABCA1, HMGCS1, NR1H3, ACAT1, PDCD1, PTGS2, CD274, CD69, MPO, HAVCR2, TAP1, ERAP1, ERAP2, AGTR2, AGTR1, PPARG, CRP, IL7, IL12A, ACE2, ELOVL6, CD38, NOS2

Prospective lung transplant cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cohort 1: Participants who received lung re-transplantation for chronic lung allograft dysfunction. Cohort 2 and 3: Participants who received first lung transplantation for end stage respiratory insufficiency.

You may qualify if:

• Lung transplant patients

You may not qualify if:

• Hyperimmunized patients
• History of auto-immune disorders

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• University of Milan: collaborator
• University of Padova: collaborator
• University of Turin, Italy: collaborator

Study Sites (4)

Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

University of Modena and Reggio Emilia

Modena, 41121, Italy

Location

University of Padua

Padua, 35131, Italy

Location

University of Turin

Torino, 10124, Italy

Location

Related Publications (3)

• Righi I, Vaira V, Morlacchi LC, Croci GA, Rossetti V, Blasi F, Ferrero S, Nosotti M, Rosso L, Clerici M. PD-1 expression in transbronchial biopsies of lung transplant recipients is a possible early predictor of rejection. Front Immunol. 2023 Jan 10;13:1024021. doi: 10.3389/fimmu.2022.1024021. eCollection 2022.

  PMID: 36703976 BACKGROUND

• Righi I, Vaira V, Morlacchi LC, Croci GA, Rossetti V, Blasi F, Ferrero S, Nosotti M, Rosso L, Clerici M. Immune Checkpoints Expression in Chronic Lung Allograft Rejection. Front Immunol. 2021 Aug 13;12:714132. doi: 10.3389/fimmu.2021.714132. eCollection 2021.

  PMID: 34489963 BACKGROUND

• Palleschi A, Gaudioso G, Edefonti V, Musso V, Terrasi A, Ambrogi F, Franzi S, Rosso L, Tarsia P, Morlacchi LC, Ferrero S, Nosotti M, Vaira V. Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome After Lung Transplantation. Transplant Direct. 2020 Apr 9;6(5):e547. doi: 10.1097/TXD.0000000000000994. eCollection 2020 May.

  PMID: 32548241 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Lung tissue, bronchoalveolar lavage

Study Officials

• Mario Nosotti, Medicine

  University of Milan, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mario Nosotti, Medicine

CONTACT

3393924679; mario.nosotti@unimi.it

Ilaria Righi, Medcine

CONTACT

+39 3470556707; ilaria.righi78@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: March 8, 2024
• Study Start: April 1, 2024
• Primary Completion: January 1, 2026
• Study Completion: February 1, 2026
• Last Updated: March 8, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data requests can be submitted starting 9 months after closing of recruitment and the data will be made accessible for up to 36 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).

Locations

IT (4)