Multifaceted features of immunoglobulin G anti‐GM1 antibodies in Guillain–Barré syndrome

Abstract

Immunoglobulin G (IgG) anti‐GM1 antibodies, the most common autoantibodies in Guillain–Barré syndrome (GBS), have diverse characteristics regarding IgG subclass, complement activation, affinity and fine specificity. In this review, an update on multifaceted aspects of IgG anti‐GM1 antibodies is provided, emphasizing their roles in creating a varying clinical picture of GBS and in developing pure motor neuropathy after antecedent infection. Diversity in IgG subclass and cross‐reactivity, both of which are closely related to the type of antecedent infection, appears to cause the variation in clinical features and severity of the disease. The environment around GM1 expression in neural tissue is thought to interfere with the binding of anti‐GM1 antibodies by modulating the immunoreactive epitope, allowing only anti‐GM1 antibodies with specific fine specificity to bind to the GM1 ganglioside. This might create the characteristic clinical picture of pure motor neuropathy in anti‐GM1‐positive GBS, although GM1 is present equally in motor and sensory nerves. The environment around the GM1 epitope on Campylobacter jejuni, the most frequently identified agent in antecedent infections of GBS, might also be important in creating diversity in the fine specificity of anti‐GM1 antibodies, possibly preventing the development of GBS in most patients with enteritis by the GM1 epitope‐bearing C. jejuni. Because there remains no direct evidence indicative that diversity of anti‐GM1 antibodies is involved in the development of GBS, further study is required.

High and Persistent Anti-GM1 Antibody Titers Are Associated With Poor Clinical Recovery in Guillain-Barré Syndrome

“…The 4 IgG subclasses (IgG1-4) are known to differ in their structure and function, affecting their pathogenicity and response to immunotherapy. 40,41 In GBS, IgG1 and IgG3 occur most frequently, and IgG1 has been associated with a more severe disease course and slower recovery. 40 The relative abundance of IgG1 and IgG3 in GBS may also explain the efficacy of IVIg in these patients.…”

“…40,41 In GBS, IgG1 and IgG3 occur most frequently, and IgG1 has been associated with a more severe disease course and slower recovery. 40 The relative abundance of IgG1 and IgG3 in GBS may also explain the efficacy of IVIg in these patients. 41 The fine specificity of anti-GM1 antibodies has also been shown to affect clinical course and outcome in GBS, and formation of ganglioside complexes has been shown to enhance or attenuate immunopathogenic effects of individual antibodies.…”

“…41 The fine specificity of anti-GM1 antibodies has also been shown to affect clinical course and outcome in GBS, and formation of ganglioside complexes has been shown to enhance or attenuate immunopathogenic effects of individual antibodies. 6,18,40 Future studies should investigate these additional aspects, for which high-throughput antibody detection using glycoarrays would be an attractive method. 42 In conclusion, high anti-GM1 IgG and IgM titers at entry and a persistent high anti-GM1 IgG antibody titer during followup are associated with poor clinical outcome in patients with GBS.…”