Two Kinds of Multiple Sclerosis May Exist


A new study from scientists at Stanford University School of Medicine published online March 28 in Nature Medicine suggests there may be two distinct versions of multiple sclerosis (MS).

Not only did the study using both animal models and human blood samples suggest two kinds of multiple sclerosis, it also found each type reacts differently to standard treatment.

According to the National Multiple Sclerosis Society MS affects 400,000 people in the United States. MS is a chronic, autoimmune, often disabling disease that attacks the central nervous system (CNS), which is made up of the brain, spinal cord, and optic nerves. Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision.

MS is triggered when immune cells, called T cells, attack the myelin sheathing, which insulates neurons in the body. Beta-interferon is often a first-line drug for MS. The study findings suggest the response to the drug may depend on which kind of MS the patient has.

In a study, Lawrence Steinman, MD and his colleagues used an established animal model of MS called experimental autoimmune encephalitis, or EAE, which they induced by injecting the animals with myelin in a way that caused the immune system to inappropriately attack the animals’ own myelin nerve-cell coatings.

A few years ago while still a PhD student at the University of Alabama, the study’s first author, Robert Axtell, had shown that, as in people with multiple sclerosis, beta-interferon can reverse paralysis in mice with EAE. But it turns out that EAE can be induced by two different autoimmune pathways, characterized by different patterns of secretion by T cells.


Like nerve cells, immune cells also communicate with one another across long distances, but they accomplish this through various chemicals called cytokines that they secrete into the blood. Immune cells on the receiving end of a cytokine “signal” may respond quite differently, depending on the particular type of cytokine to which they are exposed. Two cytokines called gamma-interferon and IL-17, for example, tend to induce the kinds of inflammatory immune-system arousal that can trigger multiple sclerosis.

Axtell, Steinman and their colleagues were able to induce two superficially similar forms of EAE in mice by directing the myelin-attacking T cells to predominantly secrete either gamma-interferon or IL-17, respectively. The researchers found that beta-interferon improved the condition of animals whose EAE had been induced by gamma-interferon-secreting T cells, but exacerbated symptoms in those whose EAE had been induced by IL-17-secreting T cells.

Intrigued, the investigators turned to humans. Brigit deJong, MD, the study’s second author, had previously been involved in research in Amsterdam in which multiple-sclerosis patients were treated with beta-interferon and meticulously followed up. The Stanford group obtained blood samples taken from 26 of these patients both before and about two years after the initiation of treatment. Without knowing which samples came from patients who had responded well or poorly to beta-interferon treatment, they went about measuring IL-17 levels in those samples.

Eventually, patients’ follow-up histories were revealed to the researchers and their measured IL-17 levels were paired with their post-treatment progress. A clear pattern emerged. Measurements of a particular variety of IL-17, called IL-17F, clustered at either very high or very low levels in individual patients’ blood. Those with very low detectable blood levels of IL-17F responded well to beta-interferon treatment, experiencing no relapses or instances of required steroids (to quickly shut down a malfunctioning immune system). But patients with very high IL-17F levels — about one out of three subjects — responded poorly by the same criteria. In fact, said Steinman, there is some evidence that beta-interferon actually worsened these patients’ conditions.

Steinman cautioned that the results need to be confirmed in larger patient groups, in his lab as well as in others. But, he said, “I think this has the potential to transform the way we take care of people with multiple sclerosis.” He said a simple, already available blood test could spare many patients the inconvenience and side effects — and spare the health-care system the expense — of a drug that most likely won’t do any good. “The other side of the coin is that beta-interferon, if it’s given only to those who are predisposed to respond to it, could turn out to be a far better drug than we ever imagined.”

T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis; Robert C Axtell, Brigit A de Jong, Katia Boniface, Laura F van der Voort, Roopa Bhat, Patrizia De Sarno, Rodrigo Naves, May Han, Franklin Zhong, Jim G Castellanos, et al.; Nature Medicine (28 March 2010) doi:10.1038/nm.2110 Article

Stanford University School of Medicine
Nature Medicine Journal



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