The common rejection module in chronic rejection post lung transplantation

Area of Science:

• Immunology
• Transplantation Medicine
• Genomics

Background:

• Solid organ transplant rejection involves shared injury mechanisms.
• A common rejection module (CRM) of 11 genes is overexpressed during acute and chronic allograft rejection.

Purpose of the Study:

• Evaluate the CRM module's utility in identifying acute rejection (AR) and chronic lung allograft dysfunction (CLAD) phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS).
• Utilize transbronchial brushings, broncho-alveolar lavage (BAL), and explant tissue for analysis.

Main Methods:

• Quantitative reverse transcription PCR (qRT-PCR) was used to measure 11 CRM gene expression in lung transplant samples.
• A geometric mean score quantified immune injury burden.
• A novel computational model was developed for key genes in lung transplant injury.

Main Results:

• Acute rejection showed significant differences in CRM gene expression, confirming prior microarray findings.
• Restrictive allograft syndrome (RAS) tissue exhibited a higher geometric mean score than donor tissue (p=0.018).
• A new 2-gene tissue CRM score distinguished RAS from BOS tissue (AUC=0.75, p=0.025), though not between BOS and RAS directly.

Conclusions:

• Transcriptional analysis of CRM genes in CLAD tissue can identify AR and differentiate RAS from BOS.
• Immune activation in RAS appears comparable to acute rejection observed in kidney, liver, and heart transplants.