GM1 IgG Autoantibody

The ganglioside GM1 is expressed in the peripheral nervous system in the nodes of Ranvier, outer myelin, and the end plates of motor neurons.² IgG antibodies against GM1 (Anti-GMI IgG) are strongly associated with motor axonal variants of Guillain-Barre syndrome.^3,4

GBS is a rapid-onset, immune-mediated demyelinating polyneuropathy associated with acute flaccid paralysis.^5,7 The initial symptoms of GBS typically involve symmetrical limb weakness and loss of tendon reflexes. Two major symptoms of GBS are defined by electrophysiological and pathological criteria.^4,6-8 The classical, demyelinating form of GBS associated with impairment of the motor or sensory nerve fibers is referred to as Acute Inflammatory Demyelinating Polyneuropathy (AIDP). A second subtype of GBS associated with the myelin or the axonal impairment is referred to as Acute Motor Axonal Neuropathy (AMAN).^6,9 AMAN is characterized by acute paralysis and loss of reflexes without sensory loss. AMAN is the most common GBS variant, accounting for as many as 5-10% of cases with much higher incidence in Asia.¹⁰

Multiple studies have found an association between AMAN and Anti-GM1 IgG seropositivity.^8,9,11-18 Certain electrophysiologic features, such as reversible conduction failure, have been associated with the presence of Anti-GM1 IgG.^13,18-21 It is thought that antibodies to GM1 bind to at the nodes of Ranvier activating complement and disrupting sodium-channel clusters and axoglial junctions, leading to nerve conduction failure and muscle weakness.⁸

The recognition that diarrheal illness can precede GBS has led some to hypothesize that an infectious agent may cause the development of Anti-GM1 IgG, possibly due to molecular mimicry resulting from antecedent infection.¹⁵ Campylobacter jejuni infection has been associated with the development of AMAN.^8,22 Several other antecedent infectious agents have been recognized including the most recently identified, Zika virus.²³