Serum antibodies targeting neurons of the monoaminergic systems in Guillain-Barré syndrome

Abstract

Guillain-Barré syndrome (GBS) is an autoimmune disease with progressive flaccid paralysis of the extremities. Several auto-antibodies have been identified, binding to myelin, gangliosides, astrocytes or proteins at the nodes of Ranvier. Some epitopes are not confined to the peripheral nerve, suggesting that auto-antibodies may also contribute to symptoms of the central nervous system, which are common in GBS and include anxiety, depression, hallucinations, oneiroid psychosis or fatigue. This notion is supported by treating patients with plasma exchange, resulting in improvement of both central and peripheral symptoms. We analyzed binding of GBS sera to neurons of cholinergic, serotonergic, dopaminergic, nor-adrenergic or histaminergic nuclei using immunohistochemistry of the rat brain. We hypothesized that GBS sera harbor antibodies against monoaminergic structures in the brain, as these circuits influence larger neuronal networks with relevance for multiple neuropsychiatric symptoms. Indeed, several GBS sera strongly and specifically reacted with monoaminergic neurons, in particular cholinergic nuclei of the diagonal band, neurons of the basal nucleus of Meynert, nor-adrenergic neurons of the nucleus coeruleus, neurons in the raphe or the ambiguous nucleus. The frequency significantly exceeded those of sera from patients with multiple sclerosis, non-autoimmune neurological disorders and healthy controls. The binding to neuronal surfaces makes it conceivable that the auto-antibodies can interfere with ion channels and receptors and thus contribute to the variable clinical spectrum of neuropsychiatric and autonomic abnormalities in GBS. Future research should include the target identification of promising GBS sera and aim to determine the functional effects of these antibodies.

Keywords: Auto-antibodies; Guillain-Barré syndrome; Monoaminergic; Neuropsychiatric.