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

LARDONE RICARDO D; IRAZOQUI FERNANDO J; NORES GUSTAVO A

Buenos Aires

Congreso; 3rd Argentinian Symposium on Glycobiology; 2019

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. 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 (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 antibodies: remarkably, 60% of these occurred without IgM antibodies of the same specificity. This unusual fact (IgG occurrence without simultaneous presence of IgM having the same specificity ~ IgG/IgM discordance) varied from 33% for anti-GM2, to 100% for anti-GT1b reactivities, and was not related to a specific type of neurological disorder. Contrary to this anti-self glycans antibody discordance, all IgG antibodies 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 antibodies could originate from pre-existing IgG recognizing structurally-related non-self glycans.