Lung Transplant Rejection
Conditions
Keywords
antibody mediated rejection, T cell mediated rejection
Brief summary
Objective: To evaluate the potential impact of molecular phenotyping of transbronchial biopsies in lung transplant recipients with allograft dysfunction, and the potential for developing a safer endobronchial mucosal biopsy format.
Detailed description
The current standard for biopsy-based diagnoses of dysfunction of lung transplants is the International Society of Heart and Lung Transplantation (ISHLT) classification applied to transbronchial biopsies, which represents an arbitrary international consensus. Recent data-driven approaches using molecular and conventional technologies indicate that this system produces frequently incorrect diagnoses with potential harm to patients due to inappropriate treatment. especially in relationship to the correct diagnosis of chronic lung allograft dysfunction is a pressing need. To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype. The MMDx, developed first in kidney transplant biopsies with thoroughly established phenotypes, will now be adapted to lung transplant transbronchial biopsies (TBBs). Microarray analysis of lung allograft biopsy specimens will be compared to conventional allograft phenotyping, including clinical, physiologic, radiographic and histological assessment. The present study will use the MMDx™ system to assess and report TBBs, and validate and refine this system in 300 unselected prospectively collected lung TBBs. A subset of the study will examine the third bifurcation mucosal endobronchial biopsies (3BMBs) paired with TBBs from 50 patients to see if the safer 3BMBs can substitute for the TBB to be used by MMDx™. Due to a considerable interest and support from participating Centers, the study is further extended and collected 1032 TBBs and 602 3BMBs from 849 patients. This this is the extension of the INTERLUNG study - INTERLUNGEX.
Interventions
PROCEDURELung transplant biopsy bites.
In the second phase of the study, two biopsy bites from the same patient will be collected to assess tissue sampling variability.
Sponsors
University of Alberta
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All lung transplant recipients undergoing a biopsy as determined by their surgeon or physician.
Exclusion criteria
* Patients who declined participation or unable to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Report the molecular scores (probability) of lung transplant disease in a reference set of 600 transbronchial biopsies. | two years | Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction. |
| Report the molecular diagnoses of the MMDx-TBB system | two years | Compare MMDx readings to standard-of-care TBB histology and clinical diagnosis of CLAD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Report the molecular scores (probability) of lung transplant disease in a reference set of 600 mucosal endobronchial biopsies. | two years | Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction. |
| Report the molecular diagnoses of the MMDx-3BMB system | two years | Compare MMDx-3BMB readings to MMDx-TBB readings and clinical diagnosis of CLAD |
| Report the molecular changes over time in medically indicated follow-up biopsies | two years | Predict and monitor response to anti-rejection treatment. |
Countries
Australia, Austria, Canada, Czechia, Poland, United States
Contacts
CONTACTKonrad S Famulski, PhD
CONTACTRobert Polakowski, PhD
PRINCIPAL_INVESTIGATORPhilip F Halloran, MD, PhD
Faculty of Medicine and Dentistry, University of Alberta
Outcome results
None listed