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.

In this paper we use a sensitive, 125I-anti-immunoglobulin-binding assay, recently adapted for use with tissue homogenates as targets, 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, and the brain autoantigen was shown to be present in equal amounts on cerebral cortex, cerebral white matter and cerebellar cortex. The autoantibodies were shown to be IgM in nature by gel filtration studies and experiments where IgM was reduced to monomers, and were found to bind equally well at 4, 20 and 37 degrees 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, but immunofluorescence studies on frozen sections revealed large amounts of immunoglobulin 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 situated in vivo. Sera from patients with multiple sclerosis were indistinguishable from normal sera in their binding to brain homogenate, and CSF from five 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, is discussed.