BY DAN HURLEY
WASHINGTON—High-dose vitamin D significantly improved immunological markers associated with relapsing-remitting multiple sclerosis (MS), investigators reported here in a platform session on Thursday at the AAN Annual Meeting. The six-month randomized trial compared high-dose vitamin D with low-dose vitamin D.
The trial involving 32 patients did not look for clinical effects, which would not likely have been evident given its relatively small size and short duration. But it is the first evidence from a randomized trial to confirm previously published observational studies, the study’s first author told the Neurology Today Conference Reporter before the session.
“The immunological changes we saw should presumably translate into a beneficial clinical effect,” said Pavan Bhargava, MD, a fellow in neuroimmunology at Johns Hopkins School of Medicine in Baltimore, MD. “But to definitely prove that, we have to wait for results from the two major clinical trials now underway.”
Dr. Bhargava and colleagues carried out the trial to see if in vitro results they published in February in the Journal of Neuroimmunology could be replicated in vivo.
They isolated peripheral blood mononuclear cells from blood collected at baseline and at six months in a randomized, double-blind trial of cholecalciferol supplementation in 32 MS patients. Fifteen of the patients received high-dose cholecalciferol (10,400 IU/day) and 17 received low-dose cholecalciferol (800 IU/day).
The high-dose group had a greater rise in serum 25-hydroxyvitamin D compared with baseline (33.67 vs. 5.35 ng/mL, p<0.0001) at the end of the study. The percentage of IL-17+ CD4+ cells in the high-dose group fell by 3.27 percent (p=0.027), whereas the low-dose group saw no significant change (-0.21%, p=0.738).
“One of the interesting observations in our study was that if you didn’t have an increase of at least 20 nanograms per milliliter, we didn’t see any change in immunologic parameters,” Dr. Bhargava said. “We only saw it when the blood level increased by at least 20 nanograms.”
In addition, the percentage of T-effector memory (TEM) cells decreased in the high-dose group by 10.4 percent (p=0.013) but not in the low-dose group (-0.7%, p=0.882). A strong correlation was noted between the decrease in TEM cells and IL-17+ CD4+ cells (Spearman's rho=0.672, p<0.001).
“The effector memory cells are of great interest,” Dr. Bhargava said. “As opposed to the central memory cells, they are thought to produce the harmful cytokines. We think those are the ones most important in MS pathogenesis.”
There are two basic types of T cells, CD4+ and CD8+, Dr. Bhargava explained. The CD4+ cells can be further divided based on their function or what molecules they produce, such as those that produce interleukin-17 (IL-17). T cells are also characterized by whether they are naïve, effector, or memory cells, which can be further subdivided into central memory and effector memory, based on whether the cells have been previously exposed to an antigen and the response they mount when re-challenged.
The study drew mixed reviews from neurologists who had the opportunity to examine the abstract data prior to Dr. Bhargava’s presentation on Thursday.
“Although the study is based only on laboratory measures, it offers proof in principle that cells known to be involved in the activation of inflammatory markers associated with multiple sclerosis are altered by achievable changes in circulating vitamin D levels,” said John R. Corboy, MD, FAAN, a professor of neurology at the University of Colorado Denver School of Medicine, co-director of the Rocky Mountain MS Center at Anschutz Medical Campus, and a member of the Neurology Today editorial advisory board.
“It is provocative,” he added, “but it will be extremely important to see data from the large clinical trials now underway.”
Timothy L. Vollmer, MD, FAAN, a professor and vice-chair of clinical research in the department of neurology at the University of Colorado Denver School of Medicine, pointed out that most successful therapies for MS target B lymphocytes rather than T cells.
“The evidence for a role of Th-17 comes only from mouse models,” Dr. Vollmer said. “Many papers suggest that changes in B lymphocytes, not IL-17, are the primary driver of functional changes in MS.”
Still, he added, “It’s interesting that they were able to see any immune effect. Now the question is whether they can look at B cells and still see an effect. That would be even more interesting.”
For more coverage of vitamin D and MS, browse our archives here.