Synthetic disialylgalactose immunoadsorbents deplete anti‐GQ1b antibodies from autoimmune neuropathy sera
2003
Summary Acute and chronic autoimmune neuropathies, including Guillain-Barresyndromes (GBS) are often character- ized by the presence of autoantibodies that react with neural gangliosides. Evidence from human and animal studies indicates that anti-ganglioside antibodies play a primary neuropathogenic role, and their rapid elimin- ation from the circulation through specific immunoad- sorption therapy thus has the potential to ameliorate the course of the disease. Here we have tested this therapeutic principle in the Miller Fisher variant of GBS that is associated serologically with acute phase anti-GQ1b ganglioside immunoglobulin G (IgG) anti- bodies, and in chronic ataxic neuropathies associated with persistently elevated immunoglobulin M (IgM) antibodies that react with GQ1b, GD3 and other disia- lylated gangliosides. Human and mouse anti-GQ1b IgG and IgM antibodies may also react with GD3, suggest- ing the shared terminal disialoside epitope could be involved in antibody binding. We thus synthesized the terminal trisaccharide, NeuAc(a2-8)NeuAc(a2-3)Gal common to GQ1b and GD3, and conjugated it to bovine serum albumin (BSA). This disialylgalactose glycoconju- gate (DSG-BSA) binds anti-GQ1b antibodies in 32/58 (55%) human sera containing IgG or IgM anti-GQ1b antibodies at titres up to 1/130 000; it also binds a wide range of mouse monoclonal anti-GQ1b and -GD3 anti- bodies. When conjugated to Sepharose as mock thera- peutic immmunoaffinity columns, the immobilized trisaccharide (DSG-Sepharose) eliminates anti-GQ1b antibodies from positive sera in proportion to their level of binding to DSG-BSA. Oligosaccharide-specific immunoadsorption therapy thus provides a new thera- peutic approach to anti-GQ1b antibody-associated syn- dromes that could be applied to clinical practice. Furthermore, modification of the immobilized oligosac- charide epitopes to incorporate other glycan structures may allow this approach to be adapted to other forms of autoimmune neuropathy associated with uniform anti-glycolipid antibody profiles.
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