Two types of HHV-6 positivity in CNS demyelinating disease

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Two types of HHV-6 positivity in CNS demyelinating disease

A new study from the University Central Hospital of Helsinki suggests that HHV-6 may have a role in progressive neurological diseases via long-term infection with demyelination. The group found that HHV-6 specific oligoclonal bands (OCBs) are found not only in MS patients, but also in other demyelinating diseases such as clinically isolated syndrome and acute disseminated encephalomyelitis. Further, their findings suggest that patients with HHV-6 specific OCBs may form a group of patients distinguishable from others with the disease.

The article, published in the Journal of Clinical Virology, surveyed a cohort of 79 patients with oligoclonal bands (OCBs) in the CSF, and revealed that patients with HHV-6-reactive OCBs (17 or 21% of the total) were significantly younger and harbored significantly more IgG-OCBs in comparison to patients without HHV-6-reactive OCBs. Both HHV-6A and HHV-6B specific OCBs were found.

Oligoclonal bands (OCBs) are bands of immunoglobulins found in a patient’s cerebrospinal fluid and serum and are often used to confirm a diagnosis of multiple sclerosis. Over 95% of MS patients have these bands in the spinal fluid (CSF). CNS infections such as chronic measles, Lyme and herpes simplex also result in oligoclonal bands. The antibodies are produced by B-cells in the CSF. When oligoclonal bands are found in the CSF but not the serum, then it is clear that the infection is localized to the central nervous system.

For decades the cause of OCBs in multiple sclerosis was considered a mystery and were not tied to specific infections. Recently, however, investigators have started to identify the infections, by finding OCBs reactive to HHV-6, EBV, and c. pneumonia. A 2013 study by Virtanen et al found 24% of 37 CSF samples from MS patients had HHV-6 reactive oligoclonal bands (OCBs), while 14% had EBV OCBs, compared to none in patients with HTLV-1 myelopathy or autoimmune encephalitis (p=0.005).

Of interest, most of the patients without OCBs had recent active infections with low HHV-6 antibody avidity while most of the patients with OCBs had high avidity (suggestive of a past infection). The OCB status in MS patients appears to be linked to HLA-DRB1, a gene that plays a critical role in the immune system. The HLA complex helps the immune system distinguish the body’s own proteins from those made by foreign invaders such as viruses or bacteria, suggesting that there may be significant differences in disease mechanisms between OCB-negative and OCB-positive MS (Mero 2013).

The authors note that HHV-6 activates T-cells via molecular mimicry (Tejada-Simon 2003) with activated T-cells reacting against myelin leading to demyelination. They note that since B cell clones are also able to react against CNS tissue of MS patients (Disanto 2012), HHV-6 may induce demyelination through both B and T-cell reaction.

For more information, read the full paper,and visit the HHV-6 Foundation’s webpage on HHV-6 & MS.