NEUROLOGICAL DISORDERS-ASSOCIATED ANTI-GLYCOSPHINGOLIPID ANTIBODIES DISPLAY DIFFERENTIALLY RESTRICTED IgG SUBCLASS DISTRIBUTION

LARDONE RD; IRAZOQUI, FJ

Buenos Aires

Congreso; . LVI reunión anual SAIB; 2020

SAIB

Antibodies against several self-glycans on glycosphingolipids are frequently detected in different neurological disorders. Their pathogenic role is profusely documented, but the keys for their origin remain elusive. Additionally, antibodies recognizing non-self glycans appear in normal human serum during immune response to bacteria. We used HPTLC-immunostaining aiming to characterize IgM and IgG subclass antibody responses against glycosphingolipids carrying self glycans (GM1/GM2/GM3/GD1a/GD1b/GD3/GT1b/GQ1b) and non-self glycans (Forssman/GA1/?A? blood group/Nt7) in sera from 27 randomly selected neurological disorder patients presenting IgG reactivity towards any of these antigens. Presence of IgG2 (p=0.0001) and IgG1 (p=0.0078) was more frequent for IgG antibodies against non-self glycans, along with a less restricted antibody response (two or more IgG subclasses simultaneously towards each given non-self glycan). Contrariwise, IgG subclass distribution against self glycans showed clear dominance for IgG3 presence (p=0.0017) and a more restricted IgG-subclass distributions (i.e. a single IgG subclass, p=0.0133). Interestingly, anti-self glycan IgG antibodies with simultaneous IgM presence had a higher proportion of IgG2 (p=0.0295). IgG subclass frequencies were skewed towards IgG1 (p=0.0266) for ?anti-self glycan A? subgroup (GM2/GM1/GD1b) and towards IgG3 (p=0.0007) for ?anti-self glycan B? subgroup (GM3/GD1a/GD3/GT1b/GQ1b). Variations in players and/or antigenic presentation pathways supporting isotype (M-G) and IgG-subclass pattern differences in the humoral immune response against glycosphingolipids carrying non-self versus self-glycans will be discussed.