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

LARDONE RD; IRAZOQUI FJ; NORES GA

Simposio; Third Argentinean Glycobiology Symposium; 2019

Different neurological disorders frequently display antibodies (abs) against several self-glycans. Although increasing evidence supports their pathogenic role, far less is known about their origin. Meanwhile, abs recognizing non-self glycans appear in normal human serum during immune response to bacteria. Using HPTLC-immunostaining, we comparatively assessed humoral immune response (IgG and IgM immunoreactivity) against glycolipids carrying self-glycans (GM3/GM2/GM1/GD1a/GD1b/GD3/GT1b/GQ1b) and non-self glycans (Gb5/GA1/?A? blood group/Nt7) in sera from 383 patients with neurological disorders along with 87 healthy controls. One-fifth of patients? sera had anti-self glycan IgG abs: remarkably, 60% of these occurred without IgM abs of the same specificity. This unusual fact (IgG occurrence without simultaneous presence of IgM having the same specificity ~ IgG/IgM discordance) ranged from 33% for anti-GM2, to 100% for anti-GT1b reactivities, and was not related to a specific neurological disorder type. Contrary to this anti-self glycans antibody discordance, all IgG abs against non-self glycans occurred simultaneously with their IgM antibody counterpart. 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 abs could originate from pre-existing IgG recognizing structurally-related non-self glycans.