g(m2)-ganglioside and Acute-Disease

Acute canine polyradiculoneuritis (ACP) is considered to be the canine equivalent of the human peripheral nerve disorder Guillain-Barré syndrome (GBS); an aetiological relationship, however, remains to be demonstrated. In GBS, anti-glycolipid antibodies (Abs) are considered as important disease mediators. To address the possibility of common Ab biomarkers, the sera of 25 ACP dogs, 19 non-neurological, and 15 epileptic control dogs were screened for IgG Abs to 10 glycolipids and their 1 : 1 heteromeric complexes using combinatorial glycoarrays. Anti-GM2 ganglioside Abs were detected in 14/25 ACP dogs, and anti-GA1 Abs in one further dog. All controls except for one were negative for anti-glycolipid Abs. In this cohort of cases and controls, the glycoarray screen reached a diagnostic sensitivity of 60% and a specificity of 97%; a lower sensitivity (32%) was reported using a conventional glycolipid ELISA. To address the possible pathogenic role for anti-GM2 Abs in ACP, we identified GM2 in canine sciatic nerve by both mass spectrometry and thin layer chromatography overlay. In immunohistological studies, GM2 was localized predominantly to the abaxonal Schwann cell membrane. The presence of anti-GM2 Abs in ACP suggests that it may share a similar pathophysiology with GBS, for which it could thus be considered a naturally occurring animal model.

Topics: Acute Disease; Animals; Biomarkers; Chromatography, Thin Layer; Diagnostic Imaging; Dogs; Electric Stimulation; Electromyography; Enzyme-Linked Immunosorbent Assay; Evoked Potentials, Motor; Female; G(M2) Ganglioside; Immunoglobulin G; Magnetic Resonance Imaging; Male; Neurologic Examination; Polyradiculoneuropathy; Sciatic Nerve; Spinal Cord; Statistics as Topic

We found that a monoclonal human IgM anti-GM2 was fixed in rat sciatic axons and Schwann cells and was able to activate human complement. The passive transfer of IgM and complement in sciatic nerves can induce an acute alteration in nerve conduction. When the transfer of IgM plus complement was repeated for 10 days, the compound action motor potential amplitude was very low and the morphological study showed axons and myelin damage. Without human complement, IgM can only slightly disorganize the myelin by separating some layers, probably by interfering with the functional role of gangliosides in the myelin package.

Topics: Acute Disease; Animals; Antibodies, Monoclonal; Autoantibodies; Chronic Disease; Demyelinating Diseases; G(M2) Ganglioside; Humans; Immunoglobulin M; Male; Neuroimmunomodulation; Rats; Rats, Sprague-Dawley; Sciatic Nerve

Guillain-Barré syndrome (GBS) sometimes is preceded by cytomegalovirus (CMV) infection. Irie et al. (J. Neuroimmunol. 1996;68:19-26) reported that three patients with GBS subsequent to CMV infection had IgM and IgG anti-GM2 antibodies. In our larger study, the IgMs from the CMV-associated GBS patients showed significantly higher anti-GM2 antibody titers than anti-GM3, anti-GD1a, anti-GD1b, anti-GD2, anti-GD3, anti-GT1b, anti-GQ1b, and anti-SGPG antibody titers. None of the anti-glycosphingolipid antibody titers differed significantly from the others in the IgGs from the CMV-associated GBS patients. However, IgM anti-GM2 antibody frequently was present in GBS patients who were not preceded by CMV infection and non-GBS patients with acute CMV infection. Our results did not support the conclusion of Irie et al. that anti-GM2 antibodies were closely associated with acute CMV infection in GBS, but acute CMV infection, with and without GBS, was associated with IgM anti-GM2 antibody.

Topics: Acute Disease; Adolescent; Adult; Antibodies, Viral; Chromatography, Thin Layer; Cytomegalovirus; Cytomegalovirus Infections; Enzyme-Linked Immunosorbent Assay; Female; G(M2) Ganglioside; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Polyradiculoneuropathy