Altered Immune Response in MS Is What May Allow Infections to Kill, Mouse Study Suggests

It is no coincidence that multiple sclerosis (MS) patients are prone to airway infections, according to research showing that MS disease processes allow suppressive immune cells to travel to the lungs and block inflammatory responses against invading viruses.

The study may offer guidance on how vaccines should be used to maximize their effectiveness against MS.

In addition to showing how autoimmune processes alter lung immunity, the research points towards a mechanism by which T-cells turn into disease-causing cells before they enter the brain and spinal cord.

The study, “CNS-targeted autoimmunity leads to increased influenza mortality in mice,” was published in the Journal of Experimental Medicine.

MS patients are four times more likely to die from infections, such as influenza, than the general population. These findings are not linked to the use of immunosuppressive drugs, studies show.

To examine how MS and infectious disease converge, researchers at Johns Hopkins University School of Medicine studied mice with experimental autoimmune encephalomyelitis (EAE) — a mouse model of MS.

Some of the mice were infected with a mouse version of H1N1 influenza, or a flu virus. The dose was adapted to make sure the mice would not die of the infection.

The study showed that all healthy mice that were infected with the flu survived. But when EAE mice were infected, 70 percent died.

To understand why, the research team, led by Katharine A. Whartenby, examined the immune processes going on in the mice’s lungs. They noted that in EAE mice with flu, an inflammatory response that is part of the innate immune system — the first-line of defense against microbes — was missing.

Immune processes further down the line — those involving T-cells — also were affected. In addition, cytotoxic T-cells, which destroy virus-infected cells, were suppressed in EAE mice.

The team traced these differences in immune response to a suppressive type of immune cell. It traveled to the lungs in EAE mice and prevented the actions of so-called co-stimulatory molecules, which help immune cells fight infection. The cells also prevented activation of T-cells.

The research team continues to study how MS impacts vulnerability to infection.

The study, funded by the National MS Society, was presented by lead author Dr. Justin Glenn at the ACTRIMS 2017 Forum last month.