Antibodies (green) against neurofascin bind to the unmyelinated nodes of Ranvier (blue) in axons (red).

Axons have an Achilles' heel that antibodies can attack to cause multiple sclerosis (MS), Mathey et al. show on page 2363.

MS is triggered when T cells breach the blood–brain barrier and produce inflammatory cytokines that activate myelin-scavenging macrophages, causing damage to the myelin sheath. Myelin-specific antibodies that enter the brain in the T cells' wake enhance the destruction of the sheath and exacerbate disease. Researchers have blamed this myelin destruction for the neurological problems of patients with MS. But in some patients, damage happens not just to the myelin, but to the axons themselves. Because myelin can be replaced, axon damage is now considered to be the cause of permanent disability.

Mathey et al. now find that some MS patients have antibodies that attack the parts of axons known as the nodes of Ranvier. These nodes must be myelin free to allow clusters of voltage-gated ion channels to propagate action potentials.

The newly identified antibodies recognized a structural node protein called neurofascin-186 (NF-186). The antibodies interrupted neurotransmission in tissue sections and worsened disease symptoms by damaging axons in a rat model of MS.

Higher levels of these antibodies were found in patients who have a particularly degenerative version of the disease. The study included only a small number of patients, but if the trend continues in larger groups, the authors will then test whether getting rid of antibody-producing B cells or filtering the antibodies out of the patients' blood might halt disease progression.