Glycoconjugates and Neuroimmunological Diseases

Abstract

A wide range of neuroimmunological diseases affect the central and peripheral nervous systems. These disorders are caused by autoimmune attack directed against structurally and functionally diverse nervous system antigens. One such category comprises peripheral nervous system (PNS) diseases, termed peripheral neuropathies, in which the target antigens for autoantibody-directed nerve injury are glycan structures borne by glycoproteins and glycolipids, particularly gangliosides that are concentrated in peripheral nerve. The archetypal PNS disorder is the acute paralytic disease, Guillain-Barré syndrome (GBS) in which autoantibodies against glycolipids arise in the context of acute infections that precede the clinical onset, notably Campylobacter jejuni enteritis. In addition, several chronic autoimmune neuropathies are associated with IgM antibodies directed against nerve glycans including sulphated glucuronic acid epitopes present on myelin-associated glycoprotein and sulphated glucuronyl paragloboside, a range of disialylated gangliosides including GD1b and GD3, and GM1 ganglioside. This chapter describes the immunological, pathological and clinical features of these disorders in the context of our broader knowledge of the glycobiology underpinning this neuroimmunological field.

Animal models for studying motor axon terminal paralysis and recovery

“…A major autoimmune disorder of the PNS is Guillain–Barré syndrome (GBS). This is an acute paralytic disorder in which autoantibodies against glycolipids or glycoproteins arise in the context of acute infections, notably Campylobacter jejuni enteritis (Yuki and Hartung ; Willison ; Sonnino et al . ).…”

Neuroinflammation in the peripheral nerve: Cause, modulator, or bystander in peripheral neuropathies?

“…These acute disorders, reaching their clinical nadir within 4 weeks of onset, are most usually driven by primary immune responses to preceding infections that are inadvertently autoreactive and target nerve plasma membrane components. In some cases, molecular mimicry between microbial and nerve glycans has been formally demonstrated to be the central component of the immunopathological reaction (Willison, ). As the primary immune response decays, or is actively suppressed by restoration of immune tolerance, the acute neuroinflammatory phase of the disorder resolves and regenerative pathways take over.…”

“…In mice, deficient in contactin‐1 in which paranodal dysfunction is present, ataxia is also a prominent feature, although this may be due to aberrant cerebellar circuitry, rather than loss of peripheral nerve afferent input (Boyle et al, ). Conversely, anti‐GM1 antibodies cause predominantly weakness without sensory loss, through targeting axolemmal GM1 in motor nerve fibers, despite the ubiquitous presence of GM1 in all nerve fibers (Willison, ). Another striking example of selective regional injury is seen in the Miller Fisher syndrome, in which the anti‐GQ1b antibodies do not injure motor nerves in the limbs but preferentially affect motor nerves innervating extraocular muscles, presumably because GQ1b is enriched in this latter site (Chiba et al, ; Liu et al, ).…”

Global and regional burden of vaccine‐associated facial paralysis, 1967–2023: Findings from the WHO international pharmacovigilance database

“…Some analyses using big data have limitations in capturing the full impact of COVID‐19 mRNA vaccines because they only include data from a few months after the introduction of the vaccines 12 . Nevertheless, the perceived risk of Bell's palsy makes people hesitant to vaccinate, 13 and the association between the vaccine and Bell's palsy remains unclear 14 …”