New seroepidemiological evidence that HHV-6 contributes to MS disease progression

Considerable biological evidence, summarized on this website, suggests that HHV-6A may be one trigger of multiple sclerosis (MS).  There also is strong evidence, most of it epidemiological, that Epstein-Barr virus (EBV) plays a role in the pathogenesis of MS (Bjornevik). There also is evidence that HHV-6A, EBV and possibly endogenous retroviruses may collaborate in the pathogenesis of MS. 

An initial demyelinating event (often, optic neuritis producing transient visual loss) may herald the subsequent development of MS, although it does not always do so. A large study from Australia followed 167 people with such a first demyelinating event, obtaining clinical data and blood samples at the time of the first demyelinating event (but not subsequently).  The team examined risk factors for conversion to MS, subsequent MS relapses and disability from MS.  The great majority of the study subjects were followed for several years.

Elevated levels of IgG antibody to HHV-6, but not anti-IgM antibody levels or HHV-6 viral load, was associated with conversion to MS and subsequent relapses of MS, although the correlation was of borderline statistical significance after multivariate adjustment for other risk factors. Elevated levels of IgG antibody to HHV-6 also were correlated with subsequent disability from MS. The titers were measured using an immunofluorescence assay kit from Panbio.

Surprisingly, EBV serological markers and viral load measurements at the time of the first demyelinating event were not predicters of the subsequent development of MS, of MS relapses or severity: indeed, higher levels of anti-EA-D-IgG were correlated with less disability from MS. 

In summary, this study fills a relative void: identifying risk factors for subsequent MS at the time of a first demyelinating event. It found evidence linking HHV-6 to MS, but the evidence was inconsistent and not robust. The lack of evidence linking EBV to MS is surprising, given persuasive previous epidemiologic studies finding a strong link. 

Read the full article: Tao 2022