Monoclonal IgMs with anti-Gal(beta 1-3) 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(beta 1-3)GalNAc and anti-Gal(beta 1-3)GlcNAc activity that bind to gangliosides GD1b and GM1, from 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(beta 1-3)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(beta 1-3)GalNAc epitopes. Both PNA and the M-proteins bound to immunoglobulin heavy and light chains, suggesting that the circulating M-proteins bind to Gal(beta 1-3)GalNAc on other immunoglobulins. These studies indicate that in addition to gangliosides the M-proteins might bind to Gal(beta 1-3)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.
Thomas
F P
FP
Neurological Institute, Columbia-Presbyterian Medical Center, New York.
Lee
A M
AM
Romas
S N
SN
Latov
N
N
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate; D003429:Cross Reactions; D004187:Disaccharides / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007136:Immunoglobulins / Q000032:analysis / Q000276:immunology; D009046:Motor Neurons; D009417:Nerve Tissue / Q000276:immunology; D009468:Neuromuscular Diseases / Q000097:blood / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000941:Antigens; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides; D000939:Epitopes; D006023:Glycoproteins; D007075:Immunoglobulin M; D007136:Immunoglobulins; C016467:Thomsen-Friedenreich antigen