MCP-1 found elevated in the CSF of patients with HHV-6B encephalopathy

A group led by Tetsushi Yoshikawa from Fujita Health University School of Medicine has identified several cytokine and chemokine responses associated with HHV-6B encephalopathy associated with exanthema subitum. The group set out to study the subset of HHV-6B encephalopathy with biphasic seizures and late reduced diffusion, a presentation that has become increasingly common among various types of HHV-6B encephalopathy at the time of primary viral infection.

Five cytokines and five chemokines were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion patients and 19 control patients with exanthem subitum without complications. Serum interleukin IL-10 (P = 0.007) and IL-8 (P = 0.025) were significantly elevated among HHV-6B encephalopathy patients compared to controls. Serum IL-10 was also significantly higher in the disease patients with sequelae compared to those without complications (P = 0.016). Interestingly, Serum IL-1β (P = 0.034) and monocyte chemoattractant protein MCP-1 (P = 0.002) were significantly higher in the controls than patients with the disease. MCP-1 has pro-inflammatory effects similar to the newly described HHV-6B chemokine U83B.

In addition, IL-10 (P = 0.012), RANTES (P = 0.001), and MIG (monokine induced by interferon γ) (P = 0.001) were significantly higher in the serum compared to CSF of the HHV-6B encephalopathy patients, while IL-6 (P = 0.034), IL-8 (P = 0.034), and MCP-1 (P = 0.001) were significantly higher in CSF than serum. The authors conclude that patients with acute encephalopathy have a unique signature of cytokines and chemokines that are consistent with a worse prognosis. Importantly, the regulation of cytokine networks in these patients appears to be quite different between peripheral blood and the central nervous system.

HHV-6B acute encephalopathy with biphasic seizures and late reduced diffusion (known as AESD in Japan) represents the largest subset of encephalopathy or 38% of cases, and is associated with a high rate (71%) of neurological disability.

In Japan, AESD begins with a prolonged febrile seizure that develops at the time of fever onset, followed by a second seizure with unconsciousness in 4–6 days after recovery from the initial seizure.

“This is an important finding because HHV-6B is the second most common pathogen in childhood encephalopathy in Japan, and the majority of the patients show a typical clinical course of AESD. Furthermore, we have not had an appropriate treatment guideline for the disease. So, elucidation of the disease pathogenesis is important for developing good treatment protocol.” said Dr. Yoshikawa “In the future I hope to develop rapid diagnostic system for HHV-6B infection and to start intervention study by using antiviral drugs to improve patient’s prognosis.” he said.

Although transplant patients with HHV-6B encephalitis are treated with antivirals routinely, no trials have been conducted to determine whether antiviral therapy might improve outcome in these patients. On the other hand, infants with symptomatic congenital CMV (HHV-5) are routinely given six weeks to six months of antiviral therapy.

The first author of this study, Dr. Yoshiki Kawamura, is the 2013 recipient of the HHV-6 Foundation’s Caroline B. Hall Young Investigator Award. Dr. Kawamura was the first to describe a case of posterior reversible encephalopathy syndrome (PRES) in a transplant recipient. The syndrome was found to be associated with HHV-6B viral reactivation and it resolved with antiviral treatment.

For more information, read the full paper, and visit the following HHV-6 Foundation webpages:

HHV-6 & Encephalitis

HHV-6 & Seizures