A new article published in PLoS One shows a significant correlation between elevated HHV-6A/HHV-6B antibody titers and relapses or progression of multiple sclerosis. Furthermore, MS patients with low titers were far more likely to stay in remission. The investigators from Hospito Clinico San Carlos in Madrid, led by Dr. Roberto Alvarez-Lafuente, analyzed the titers of IgG and IgM antibodies against HHV-6A and HHV-6B in over 300 MS patients treated with three standard MS treatments and followed them for two years. Treatments included IFN-beta, glatiramer acetate, and natalizumab.
The group found that 129 of 187 (69.0%) MS patients with decreasing HHV-6A/B IgG antibody titers after 2-years of therapy had no relapse or progression, compared with only 46 of 113 (40.7%) of MS patients with increasing HHV-6A/B IgG antibody titers (p = 0.0000015); statistically significant differences were found for each of the three treatments studied, but the highest significance was found for patients on natalizumab.
Furthermore, the group noted that HHV-6A/B IgG antibody titers reached their highest value two weeks before the relapse (p = 0.0142), whereas HHV-6A/B IgM antibody titers reached their highest value one month before the relapse (p = 0.0344). Similar to what occurred during progression, the group also found that higher titers of anti-HHV-6A/B IgG at 24-month visit were significantly associated with a higher likelihood of relapse during the two-year course of treatment. The mechanism of action for glatimir acetate, an acetate salt, is not completely understood. Natalizumab is a monoclonal antibody that selectively binds to a specific component of adhesion molecules on lymphocytes, monocytes and eosinophils, which in turn inhibits interaction with VCAM-1, and is thus thought to prevent leukocyte migration into the central nervous system.
In patients receiving IFN-beta treatment, the study found that 16 of 38 (42.1%) patients with an increase of HHV-6A/B IgG antibody titers were clinical responders vs. 39 of 50 (78%) MS patients with a decrease of HHV-6A/B IgG antibody titers (p= 0.0006). In addition, 4 of 21 (19%) patients with an increase of HHV-6A/B IgG antibody iters >20% were clinical responders, compared to a staggering 13 of 16 (81.2%) patients with a decrease of HHV-6A/B IgG titers .20% (p =0.0002). Interferon-beta treatment is used as an antiviral therapy and is thought to have immunomodulating properties. Patients who had developed antibodies to interferon-beta were excluded from the analysis.
Dr. Alvarez-Lafuente ‘s group has previously shown that HHV-6 DNA could be found in MS patient serum during exacerbations but not during remissions (Alvarez-Lafuente 2006, Alvarez-Lafuente 2004). However, studies of HHV-6 antibodies in MS have been mixed with some showing a correlation (Ben Fredj 2013, Ablashi 2000, Soldan 1997, Simpson 2012) and inconsistent with others (Simpson 2014, Engdahl 2014). Several dozen studies have sought to determine the relationship between HHV-6 reactivation and MS status or clinical course with varying results, dependent on the material used, the marker studied, the timing of sample collection (before, during, or after relapse), and the assay’s sensitivity.