Glycolipid antigens and autoantibodies in autoimmune neuropathies

• In GBS, a proceeding infection results in the development of antiganglioside antibodies.
• Molecular mimicry between microbial and self-glycans is an underlying mechanism.
• B cell tolerance to self glycans is overcome when generating this immune response.
• Some antiglycolipid antibodies only react with heteromeric pairs of glycolipids.

Autoantibodies to glycans present on glycolipids mediate the postinfectious paralytic disease, Guillain–Barré syndrome (GBS). These glycans are also found on lipo-oligosaccharides (LOSs) of GBS-inducing microbes, suggesting molecular mimicry as a mechanism for disease induction. How B lymphocyte tolerance to self-glycans is regulated during the initiation phase of the disease is currently under investigation. The discovery of antiglycolipid antibodies that bind to heteromeric glycolipid complexes has generated new insights in this field. Heteromeric complexes are structurally distinct glycolipids that interact to form new molecular shapes capable of either enhancing or attenuating recognition by autoantibodies. Although the principles emerging from this phenomenon have a substantial impact on diagnostics methods, they also raise intriguing questions about the diversity of innate antibody repertoires, mechanisms of tolerance, and autoantibody targeting of neural membranes.