Most of anti-glycolipid IgG-antibodies associated to neurological disorders occur without their IgM counterpart

Abstract

Background Different 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. Methods Using 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. Results In 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. Conclusions Classic 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. Electronic supplementary material The online version of this article (10.1186/s12929-019-0562-5) contains supplementary material, which is available to authorized users.

Neurological disorders-associated anti-glycosphingolipid IgG-antibodies display differentially restricted IgG subclass distribution

“…As already observed, anti-non-self glycan IgG antibodies always had their IgM counterpart 17 , and presented a less restricted IgG subclass response (i.e. two or more different IgG subclasses).…”

“…Although recent work on IgM and IgG isotypes has extended this view to explain the origin of other anti-self glycosphingolipid antibodies associated with neurological disorders 17 , some questions persist. These types of IgG antibodies are absent in healthy humans 6,17 . Polysaccharides, some other nonprotein antigens (e.g.…”

Abnormal antibodies to self-carbohydrates in SARS-CoV-2 infected patients

“…Autoantibodies to self-glycans are associated with a variety of autoimmune disorders. 57,[76][77][78] For example, antibodies to gangliosides are often linked to neurological disorders such as Guillain-Barre Syndrome (GBS) and Miller Fisher Syndrome. Gangliosides are expressed at high levels on nerve cells, and antibodies to these glycans can have a variety of effects, including destruction of the neuromuscular junction of nerve cells and disruption of the blood-nerve barrier and/or blood-brain barrier.…”

“…While very uncommon in healthy individuals, anti-glycolipid antibodies are often found in populations that have autoimmune diseases and other nervous system dysfunctions. 57 For example, antibodies to asialo-GM1, GM1a, GD1a, and GD1b are frequently observed in patients with Guillain-Barre Syndrome (GBS). We observed unusually high antibodies to GBS glycans in 15% of patients ( Figure 2A).…”