Coppe Labs to offer mRNA, ciHHV-6 testing and Immunohistochemistry for HHV-6
Three important tests for HHV-6 will now be available at Coppe Labs, including two that are not available commercially at any other location: the mRNA test for assessing active infection and immunohistochemistry analysis for biopsy samples. The company will utilize the reverse transcription polymerase chain reaction (RT-PCR) technique as opposed to traditional DNA PCR, in an effort to document active replication of the virus (Pradeau 2006).
Although plasma HHV-6 DNA load correlates with active infection, only a test of mRNA can differentiate between active and latent infection in a patient with chromosomally integrated HHV-6 (ciHHV-6). Therefore, transplant physicians must currently use clinical judgment rather than viral load analysis in making a decision to treat a symptomatic patient with ciHHV-6. This test should prove to be invaluable for transplant physicians, since failure to treat can result in HHV-6 encephalitis or other serious manifestations, while antivirals can cause serious side effects such as bone marrow suppression or kidney toxicity.
In addition, Coppe Lab’s HHV-6 immunohistochemical (IHC) staining will help detect the presence of HHV-6 proteins in a variety of fixed and paraffin embedded tissues, thereby confirming not only that the virus is present, but also which cells contain the virus and whether the infection is active or latent. In addition, the IHC test will be able to determine if the infection is caused by HHV-6A and HHV-6B.
One reason to test biopsy samples for HHV-6 is that this is a highly cell associated virus that does not always circulate in the plasma once it has become persistent in tissues. Recent studies have reported active HHV-6 infection in the heart, brain and liver, in the absence of plasma viremia (Leveque 2011, Buyse 2013). Identifying HHV-6 proteins in tissue samples allows for the definitive diagnosis of tissue infection, since only replicating virus will produce late structural proteins.
Coppe Labs will also offer a hair follicle test to determine ciHHV-6 status. It is not possible to differentiate ciHHV-6 patients from those with active infection using a plasma PCR DNA test. However, a simple whole blood PCR DNA test can identify a ciHHV-6 patient in all situations except an acutely ill patient with encephalitis, GVHD or DRESS/DIHS (conditions associated with extremely high HHV-6 DNA loads). CiHHV-6 patients typically have whole blood DNA loads of over 2 million copies/ ml or several loads higher than the expected viral load in a transplant patient with reactivation. The Coppe hair follicle test could definitively identify an acutely ill ciHHV-6 patient.
The University of Washington also has a new ddPCR test for ciHHV-6. This test utilizes a third generation PCR technique that can compare the number of DNA genomes to the number of cells in a whole blood sample, with a high degree of precision. A ratio of 1:1 in a whole blood sample (but not a plasma sample) is considered definitive test of ciHHV-6 status. However, the University of Washington test cannot determine if the ciHHV-6 patient has actively replicating HHV-6 and requires treatment.
Recently, evidence has emerged that the integrated HHV-6 in ciHHV-6 individuals can activate under conditions of extreme immunosuppression (Endo 2014) and in pregnancy (Gravel 2013).
Coppe Labs is a CLIA-certified laboratory that specializes in HHV-6, EBV, CMV and HHV-7. David Baewer, MD, PhD, who completed training in anatomic and clinical pathology at Johns Hopkins, serves as their on-site medical director. The lab was founded by Konstance Knox, PhD and Donald Carrigan, PhD, who have been publishing on HHV-6 since the early 90’s and previously co-directed a laboratory diagnostic research initiative known as Wisconsin Viral Research. They also established a mRNA test for HHV-6 that was offered through Viracor from 2000-2002.
Click here to learn the HHV-6 tests offered by Coppe Labs or visit Coppe Labs website.
Click here to learn more about ciHHV-6 testing.