ORGAN-SPECIFIC IGM AUTOANTIBODIES TO LIVER, HEART AND BRAIN IN MAN - GENERALIZED OCCURRENCE AND POSSIBLE FUNCTIONAL-SIGNIFICANCE IN NORMAL INDIVIDUALS, AND STUDIES IN PATIENTS WITH MULTIPLE-SCLEROSIS

Abstract

A sensitive 125I-anti-Ig-binding assay, recently adapted for use with tissue homogenates as targets, was used to demonstrate autoantibodies to brain, liver and heart in the sera of normal persons. Quantitative absorption analyses demonstrated that the autoantigens detected were in each case organ-specific; the brain autoantigen was present in equal amounts on cerebral cortex, cerebral white matter and cerebellar cortex. The autoantibodies were IgM in nature by gel filtration studies and experiments where IgM was reduced to monomers, and bound equally well at 4, 20 and 37.degree. C. Cross-reactions with brain, liver and heart of rat and dog were unpredictable and usually weak. Parallel studies with kidney homogenates failed to detect anti-kidney autoantibodies; immunofluorescence studies on frozen sections revealed large amounts of Ig in normal kidneys, mainly on glomerular and tubular basement membranes, raising the possibility that autoantibodies to kidney are present but that the autoantigen sites are saturated in vivo. Sera from patients with multiple sclerosis were indistinguishable from normal sera in their binding to brain homogenate; CSF from 5 patients with multiple sclerosis did not bind at all to brain homogenate. The theoretical and practical significance of multiple IgM autoantibodies in normal persons and the organ specificity of the autoantibodies are discussed.