How Do You Anticipate Allograft Rejection?

Transplant recipients require frequent monitoring after transplant to assess the ongoing health of their transplanted organs. Following the transplant, recipients must adhere to a complex regimen of immunosuppressive medications, many with potential side effects, including infection and drug toxicities, to maintain a healthy transplanted organ.

Protocols for the current standard of care for post-transplant monitoring typically rely on serial monitoring of immunosuppressive drug levels; serum or enzyme testing; painful, expensive, and invasive surveillance biopsies; and the clinical appearance of rejection symptoms, indicating early allograft rejection. These insensitive, late-trailing indicators of graft function may not appear until significant organ damage occurs, leaving clinicians and patients with fewer options to improve organ health before more severe complications occur.

TruGraf intro stain

A New Approach: Blood Gene Expression Profiling

Transplant Genomics’ approach to the management of transplant patient care is based on precision medicine. Precision medicine hinges on the ability to characterize individuals based on a wide range of molecular and phenotypic data—genomic, epigenomic, proteomic, and other—that together convey a more accurate image of diagnosis that is personalized and multifaceted.

TruGraf is a non-invasive test that measures differentially-expressed genes in the blood of transplant recipients to identify patients who are likely to be adequately immunosuppressed and, in doing so, rule out graft damage. TruGraf® measures the difference in gene expression for a precise panel of specific genes that have been empirically determined to discriminate between allografts that are truly healthy (Transplant eXcellence, or TX), and those in transplant patients that are ”silently” subclinically rejecting (not-TX) with no other suspicion of rejection. 

  • Transplant eXcellence (TX) means that the transplanted organ is expected to be adequately immunosuppressed 
  • not-TX means that the transplant organ is likely to be inadequately immunosuppressed.
Rejection Heat Map

The figure above is a heat map representation of gene expression levels (red = high; blue = low) for 1,000 genes in 350 kidney biopsy samples from patients classified into diagnostic categories based on conventional histological analysis. The molecular phenotypes displayed show a strong correlation to graft status and complement the histological analysis, resolving ambiguous or borderline results. Molecular signatures for each diagnostic category were discovered through an unbiased approach involving global gene expression studies. More than 2,000 genes (including cellular receptors, cytokines, and signaling molecules) were discovered to be differentially expressed in kidney biopsies and mapped back to over 60 distinct immunological pathways. The ~120 genes with the highest discriminatory power between the non-TX and TX phenotypes are the IP incorporated in TruGraf.

Medical professionals may use TruGraf tests to:

  • monitor patients to detect “silent” subclinical acute rejection
  • inform when to perform for-cause biopsies, rather than relying on protocols or waiting for creatinine levels to rise
  • optimize minimization of immunosuppression therapy by ensuring early detection of an immune response
  • profile biopsies to complement conventional histology and help resolve ambiguous or borderline cases.