Abstract
BackgroundDifferent neurological disorders frequently display antibodies against several self-glycans. Increasing evidence supports their pathogenic role; however, far less is known about their origin. Meanwhile, antibodies recognizing non-self glycans appear in normal human serum during immune response to bacteria.MethodsUsing high performance thin layer chromatography-immunostaining, we comparatively evaluated humoral immune response (IgG and IgM immunoreactivity) against glycolipids carrying self-glycans (GM3/GM2/GM1/GD1a/GD1b/GD3/GT1b/GQ1b) and non-self glycans (Forssman/GA1/“A” blood group/Nt7) in sera from 383 patients with neurological disorders along with 87 healthy controls.ResultsIn contrast to no healthy controls having anti-self glycan IgG antibodies, one-fifth of patients’ sera had anti-self glycan IgG antibodies: remarkably, 60% of these occurred without IgM antibodies of the same specificity. Contrary to this unusual fact (anti-self glycan IgG occurrence without simultaneous presence of IgM having the same specificity ~ IgG/IgM discordance), all IgG antibodies against non-self glycans occurred simultaneously with their IgM antibody counterpart (i.e. 0% discordance). When analyzed closer, the IgG/IgM discordance frequency for anti-self glycans exhibited a dual trend: below 40% for IgG antibodies against GM2, GM1 and GD1b, and greater than 53% for IgG antibodies against the remaining self glycans. Interestingly, this discordance behavior was common to several different neurological disorders.ConclusionsClassic immunology principles indicate this anti-self glycan IgG/IgM discordance should not occur in an antibody response; its unusual presence is discussed within the “binding site drift hypothesis” context, where anti-self glycan IgG antibodies could originate from pre-existing IgG recognizing structurally-related non-self glycans.
Highlights
Different neurological disorders frequently display antibodies against several self-glycans
A similar origin is described for IgM antibodies against a few self glycan-carrying glycolipids such as gangliosides GM1 and GD1b [6], these normal antibodies are of Lardone et al Journal of Biomedical Science (2019) 26:67 low affinity and non-pathogenic [7]
In a general screening searching for anti-glycolipid antibodies in neurological disorders, we analyzed serum samples from 383 patients, along with sera from 87 healthy controls
Summary
Different neurological disorders frequently display antibodies against several self-glycans Increasing evidence supports their pathogenic role; far less is known about their origin. Antibodies recognizing non-self glycans appear in normal human serum during immune response to bacteria. Infection of specific serotypes of Campylobacter jejuni cause Guillain-Barré syndrome associated with the presence of anti-GM1 antibodies [11]. These serotypes contain lipooligosaccharides carrying GM1-glycan (terminal tetrasaccharide) that can induce production of anti-glycan IgG-antibodies recognizing ganglioside GM1 (“molecular mimicry” hypothesis) [12]. Little is known about the origin of several other anti-self glycolipid antibodies associated to neurological diseases, especially for those having no “normal” IgM-antibodies [7]
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