Transplant Testing for Human Herpesviruses
Coppe Laboratories’ scientists have a long history in the study and diagnosis of viral infections in transplant patients. Drs. Knox and Carrigan were among the first scientists to correlate symptoms of pneumonitis, encephalitis, and graft failure in bone marrow transplant recipients with reactivation of HHV-6.
Until now, testing for HHV-6 has lacked the specificity for differentiating between latent and active infection. Coppe Laboratories performs reverse transcription polymerase chain reaction (RT-PCR) which is a a sensitive and powerful tool for analyzing active, replicating virus.
Coppe Laboratories is currently the only reference laboratory performing comprehensive testing for chromosomally integrated HHV-6 (ciHHV-6) on blood, hair follicle and nail clippings.
We are also currently the only reference laboratory providing immunohistochemical staining of tissues to denote active HHV-6 infection.
People with some chronic illnesses (including tick-borne illnesses) are at high risk of suffering additional viral and bacterial infections because of their immune system dysfunction.
CMV, EBV, HHV-6A and HHV-6B are all members of the human herpesvirus family. HHV-6 infects nearly all people before the age of 2 and in children it causes a disease called roseola. HHV-6 and the other herpesviruses establish life-long infection, and while they are usually maintained in a dormant or “latent” state, they can become active again especially during times of immune dysregulation. The symptoms of HHV-6 related illness closely mimic those of Lyme disease. For patients experiencing long-lasting symptoms, testing for these viruses is warranted. Because nearly every person has latent HHV-6, it is imperative that testing is done to establish if the virus is activated. Testing performed at most laboratories cannot distinguish between the latent virus and active HHV-6.
Coppe Laboratories performs testing that determines active infection for HHV-6 and we are the only reference laboratory to provide that testing. For more information please review the testing for HHV-6.
HHV-6 in relation with Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). The origin of MS is still unclear despite the many studies that have been conducted. Viruses have long been implicated as contributory factors in MS and may play a role at the onset of symptoms, during the development of the disease, and may trigger the exacerbations that are commonly seen with relapsing-remitting multiple sclerosis (RRMS).
Human herpesvirus 6 (HHV-6) is one of the viral agents implicated in MS, and relapses can range from very mild to severe enough to interfere with a person’s ability to function on a day-to-day basis. Our CEO, Dr. Konstance Knox, was among the first scientists to identify HHV-6 infected cells in the brains of persons with MS and correlate HHV-6 reactivation with clinical relapse in MS patients. The virus is widely prevalent in the human population, and primary infection usually takes place in the first years of life. However, the virus remains latent and only reactivates under certain conditions.
Coppe Laboratories’ commercial assays are highly sensitive and specific in detecting viral expression that signals active infection. Our testing also looks at the subset of patients that carry an inherited form of the virus (ciHHV-6). Coppe Laboratories is currently the only reference laboratory offering this testing.
- Debue, S, et al; Future Virology, 2012: 7(9) The Long and Evolving Relationship Between Viruses and Multiple Sclerosis
- Owens G. et al; Neuroscientist December 2011 17: Viruses and Multiple Sclerosis
- Knox, K. et al; Clin Infect Dis. (2000) 31 (4) Human Herpesvirus 6 and Multiple Sclerosis: Systemic Active Infections in Patients with Early Disease
HHV-6 in relation to Chronic Fatigue Syndrome (CFS)
Several studies have indicated HHV-6 as a trigger for the syndrome. Although the role of HHV-6 in chronic fatigue syndrome is an area of ongoing investigation, HHV-6 reactivation and various degrees of central nervous system dysfunction have been observed in CFS sufferers. In both MS and chronic fatigue syndrome (CFS) patients, increased levels of the HHV-6 antibody, presence of viral DNA and alterations in host cellular immune response have been reported.
- Komoroff AL, J Clin Virol. 2006 Dec;37 Is human herpesvirus-6 a trigger for chronic fatigue syndrome?
Chromosomally Integrated HHV-6
HHV-6 exists in a chromosomally integrated form (ciHHV-6) whereby the viral DNA resides in every somatic and germ cell in the body. Patients with ciHHV-6 have been misdiagnosed and unnecessarily treated with powerful and toxic antiviral agents based on a mistaken diagnosis of reactivated HHV-6. High persistent HHV-6 DNA levels in blood can be found in immunocompetent individuals with viral chromosomal integration. Analysis for integration is a necessary first step in distinguishing between ciHHV6 and HHV-6 reactivation.
The second necessary step for identifying HHV-6 reactivation in a ciHHV6 patient is confirmation of viral gene expression using mRNA detection. RT-PCR for mRNA can distinguish an active herpesvirus infection from a latent infection. In addition, it is difficult to evaluate response to antiviral therapy in a ciHHV-6 patient because the high level of DNA from ciHHV-6 overwhelms and masks viral DNA produced by reactivated virus. mRNA testing can be used to evaluate the efficacy of antiviral therapy in a ciHHV-6 patient.
The ciHHV-6 panel from Coppe Laboratories
ciHHV6 occurs in about 1% of the population and confounds the diagnostic interpretation of reactivated HHV-6 in solid organ and hematopoietic transplant recipients (SOT and HCT). In the case of an HCT recipient or donor who has undiagnosed ciHHV6, the evolution of chimerism due to stem cell engraftment can be misdiagnosed as HHV-6 reactivation during the early engraftment period and patients may be treated inappropriately. Conversely, in the case of pre-identified ciHHV6 HCT or SOT recipients, the high background level of DNA from integrated HHV-6 can mask HHV-6 reactivation and make it impossible to evaluate the efficacy of antiviral therapy.
The ciHHV-6 Test Panel from Coppe Laboratories can identify active infection in a ciHHV-6 individual.