LGC Clinical Diagnostics Blog

Managing Transplant Patient Health with Molecular Diagnostics

Written by Eric Morreale, PhD | December 16, 2024 at 8:30 PM

Infectious complications are a significant concern for patients after solid organ transplants (SOT). Viruses are a common cause of these infections, which are often the reason for post-operative transplant rejection, malignancy, morbidity, and mortality. While a healthy person’s immune system can likely control the viruses, transplant patients taking immunosuppressive medications likely can’t.

Latent DNA viruses in transplant patients may reactivate after they begin their immunosuppressive regimen and can cause disease or problems with the transplant within the first six months,1 making early detection and treatment critical. Molecular testing is a vital tool to achieve that goal.

Key viral threats in post-transplant care

Numerous viruses can lead to infections post-transplant, but the three most common are cytomegalovirus (CMV), Epstein–Barr virus (EBV), and BK polyomavirus (BKV).

Cytomegalovirus (CMV)—a DNA herpesvirus

Reactivation of CMV is a risk factor for rejection and other opportunistic infections, including fungal infections. CMV infection can affect up to 60% of patients with CMV IgG D+/R−, and 5% to 30% of those with CMV IgG R+.1 It may present as CMV syndrome, which includes fever, fatigue, and leucopenia. Some patients may experience tissue-invasive CMV diseases, such as pneumonitis or gastritis.

Epstein–Barr virus (EBV)—an oncogenic γ-herpesvirus

Individuals may acquire EBV infections in infancy or adolescence. It can reactivate or be transmitted from the allograft to organ transplant patients. EBV-positive transplant recipients can develop post-transplant lymphoproliferative disorder (PTLD) within the first year after transplant, and EBV-negative recipients 5 to 15 years after transplant. EBV infection can present as mononucleosis, hepatitis, pneumonitis, lung mass, lymphadenopathy, or gastrointestinal disease.4

BK polyomavirus (BKV)—a DNA virus of the Polyomaviridae family

After a transplant, BKV can cause hemorrhagic cystitis, tubulointerstitial nephritis, ureteric stricture, BKV-associated nephropathy, and premature graft failure. It may remain latent in renal tubular epithelial cells.4 BKV is of particular concern for kidney transplants. It’s estimated that 4% to 8% of kidney allografts may fail because of BKV.5

Molecular tests put critical information in clinicians’ hands

Transplantation is a complex, life-saving procedure. Traditional methods for monitoring the graft after transplantation (e.g., non-specific markers, surveillance, and biopsies) are “invasive, expensive, and limited by subjective interpretation.”5 Non-invasive assays, particularly molecular viral diagnostic assays, provide clinicians with critical information to improve outcomes and organ rejection rates. Molecular diagnostic test benefits such as handling high volumes of samples and the lack of decay make them a wise choice.

Post-transplantation monitoring confirms that the transplant is functioning correctly. Biomarkers can predict graft rejection and evaluate immunosuppressive therapy effectiveness, helping minimize patient risk. Quantifying viral load over time offers clinicians a series of test results for making timely decisions about antivirals--when to start, when to end, or when to adjust dosages.

Quantitative molecular diagnostic tests’ role in transplantation 

  • Diagnose acute infectious syndrome
  • Monitor for viral infection and recurrence
  • Predict disease severity
  • Determine viral suppression success
  • Detect antiviral resistance (viral load increases or decreases)

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115029/

Trust your results

The ongoing and time-sensitive nature of monitoring post-transplantation patients requires a high level of confidence that assays are performing as needed. Third-party controls’ impartiality and mimicking of patient samples make them the better choice over instrument manufacturer controls.

Comparing third-party controls? Ask the following questions:

  • Do they rely on a patient-like control matrix? Do they mimic authentic patient samples?
  • Are they full-process controls designed to detect errors at every stage, from sample prep to detection?
  • Are they targeted near the clinical decision point (low positives truly test an assay’s performance)?
  • Are they ready to use and not need manipulation, which can create errors and workflow delays?
  • Are they stable with a long shelf-life that helps manage inventory and reduces waste?
  • Are they available in large lot sizes to allow your lab to perform long-term quality control monitoring?
  • Does the vendor have a track record of supporting clinical labs’ needs? Can they meet supply demands and provide technical support when needs fluctuate?

Introducing our latest product:

ACCURUN® 350 CMV DNA Positive Control is a full-process, third-party control that supports ongoing assay monitoring for routine patient testing of CMV molecular assays. This product is a ready-to-use, low-positive quality control solution that is designed to detect subtle performance changes at the lower limits of detection. This product contains cultured virus that is reactive for CMV DNA that is diluted in defibrinated plasma.

AccuSpanTM linearity panels

SeraCare’s AccuSpanTM linearity panels span the dynamic range of quantitative infectious disease assays and evaluate instrumentation analytical sensitivity. They challenge assay performance at defined intervals to ensure consistency throughout the linear range Our linearity panels can be used to establish the reportable range during assay verification, which is a CLIA requirement. These panels are useful in validation procedures for new assay implementation, operator training, and troubleshooting signs of assay deterioration.

CMV Linearity Panel:

The AccuSpanTM CMV DNA Linearity Panel is a nine-member panel comprising seven members representing serial log dilutions of cultured CMV , with established reactivity for CMV DNA, in CMV DNA negative diluent. The target concentration of this panel is 20 - 20,000,000 IU/mL. This panel also consists of one negative member prepared from the diluent and one member of diluent to perform additional dilutions as desired. The diluent was prepared from normal human plasma.

BKV Linearity Panel:

The AccuSpanTM BKV Linearity Panel is a seven-member panel comprising six members representing serial log dilutions of cultured BK virus, with established reactivity for BKV DNA, in BKV DNA negative diluent. The target concentration of this panel is 200 - 20,000,000 IU/mL. This panel also consists of one negative member prepared from the diluent. The diluent was prepared from normal human plasma.

EBV Linearity Panel:

The AccuSpan™ EBV Linearity Panel is an eight-member panel consisting of seven members representing serial log dilutions of cultured EBV with established reactivity for EBV DNA, in EBV DNA negative diluent. The target concentration of this panel is 50 - 50,000,000 IU/mL. This panel also consists of one negative member prepared from the diluent. The diluent was prepared from normal human plasma.

 

To learn more about the importance of infectious disease testing for the clinical management of transplant recipients, please read our white paper:

 

Our quality measurement tools are some of the most respected in the industry and are relied upon by many world-class laboratories to ensure assay performance. Improve confidence in your test results.

Contact Us: 800-676-1881 • CDx-sales@lgcgroup.com

 

______________________________________________________________________________________________

Sources

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312768/
  2. https://diagnostics.roche.com/global/en/article-listing/health-topics/infectious-diseases/transplant-transmitted-infections.htmlhttps://diagnostics.roche.com/global/en/article-listing/health-topics/infectious-diseases/transplant-transmitted-infections.html
  3. https://journals.lww.com/co-infectiousdiseases/fulltext/2017/12000/viral_infections_in_solid_organ_transplant.10.aspx
  4. https://pubmed.ncbi.nlm.nih.gov/30072213/
  5. https://onlinelibrary.wiley.com/doi/full/10.1111/iji.12654#:~:text=Its%20main%20aim%20is%20to,plan%20to%20optimize%20the%20patient's
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115029/
  7. https://diagnostics.roche.com/global/en/article-listing/health-topics/infectious-diseases/transplant-transmitted-infections.htmlhttps://diagnostics.roche.com/global/en/article-listing/health-topics/infectious-diseases/transplant-transmitted-infections.html
  8. https://pubmed.ncbi.nlm.nih.gov/30072213/