Neuronal endocytosis of anti-ganglioside antibodies: implications for Guillain-Barré syndrome.

Abstract

This scientific commentary refers to ‘Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis’, by Cunningham et al. (doi:10.1093/brain/aww056). Guillain-Barre syndrome (GBS) is an acute disorder primarily of the peripheral nervous system that yearly affects ∼100 000 people worldwide. GBS is characterized by a rapidly progressive but variable degree of muscle weakness with or without sensory disturbances (van den Berg et al. , 2014). Patients may develop respiratory failure for which they require artificial ventilation. After a period of variable duration and supported by treatment with intravenous immunoglobulin (IVIg) or plasma exchange, patients start to recover, but recovery is often incomplete. GBS represents a spectrum of different subtypes, including regional variants and in rare cases even involvement of the CNS. The acute onset and monophasic disease course can be explained by the preceding infection that triggers a transient immune response to peripheral nerves. Various types of infections are associated with GBS, including Campylobacter jejuni , cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae , and hepatitis E virus. More recently Zika virus has been suggested to be related to GBS, but this possible association requires further investigation (Cao-Lormeau et al. , 2016). In the acute phase, serum antibodies against various gangliosides present in human nerves can be found in about half of all patients with GBS. Molecular mimicry is one mechanism by which preceding infections may trigger the production of cross-reactive antibodies to gangliosides, as has been demonstrated convincingly for C. jejuni -related GBS. Important questions remaining are why antibodies to gangliosides are not found in all patients with GBS and why some patients may even show signs of CNS involvement. In this issue of Brain , Cunningham and co-workers provide compelling evidence that anti-ganglioside antibodies are endocytosed at the nerve terminals, removed from the systemic circulation and transported …