Basic proteins bind immunoglobulin G: a mechanism for demyelinating disease?
Heat-aggregated immunoglobulin G ( HAGG ) bound avidly to solid-phase basic proteins, including myelin basic protein. In contrast, monomeric immunoglobulin bound weakly. Bound HAGG could activate complement. Normal human serum strongly inhibited the binding of HAGG , even when decomplemented or greatly diluted. Cerebrospinal fluid was also inhibitory, but the effect was weaker. Apart from inhibition by decomplemented serum, the biochemical characteristics of the interaction were similar to those of other Fc ligands with IgG, particularly C1q. In multiple sclerosis this interaction could occur between IgG and central-nervous-system myelin basic protein, leading to demyelination by activation of immune mechanisms of tissue damage. Bound IgG is present in multiple sclerosis plaques and IgG from multiple sclerosis patients can produce demyelination in experimental models. However, there is little evidence of any specific immunity to central-nervous-system antigens in multiple sclerosis, and this non-specific interaction might be an important link in the pathogenesis of the disorder.
D001769:Blood; D002555:Cerebrospinal Fluid; D003166:Complement Activating Enzymes / Q000276:immunology; D003167:Complement Activation; D015922:Complement C1q; D003176:Complement C3 / Q000276:immunology; D015932:Complement C3c; D006358:Hot Temperature; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism*; D011485:Protein Binding
D003176:Complement C3; D007074:Immunoglobulin G; D004676:Myelin Basic Protein; D015922:Complement C1q; D015932:Complement C3c; D003166:Complement Activating Enzymes