Monoclonal IgMs with anti-Gal(β1-3)GalNAc activity in lower motor neuron disease; identification of glycoprotein antigens in neural tissue and cross-reactivity with serum immunoglobulins

IgM monoclonal antibodies (M-proteins) with anti-Gal(β1-3)GalNAc and anti-Gal(β1-3)GlcNAc activity that bind to gangliosides G_D1b amd G_M1, frpm two patients with lower motor neuron disease were tested for binding to neural glycoproteins. The M-proteins bound to several glycoproteins in the central and peripheral nervous system including to some in the non-myelin or axonal fraction only. Peanut agglutinin (PNA) which is specific for Gal(β1-3)GalNAc, bound to the same protein bands. Since serological studies revealed that the M-proteins were complexed to IgG, serum immunoglobulins were tested for presence of Gal(β-3)GalNAc epitopes. Both PNA and the M-proteins bound to immunoglobulin heavy and light chains, suggesting that the circulating M-proteins bind to Gal(β1-3)GalNAc on other immunoglobulins. These studies indicated that in addition to gangliosides the M-proteins might bind to Gal(β1-3)GalNAc bearing glycoproteins in vivo and that carbohydrate epitopes on immunoglobulins might have a role in the development and regulation of autoantibodies which cross-react with neural antigens and may cause neurological disease.