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Many sera from normal individuals as well as patients with various disease states contain agglutinating antibodies which show specificity for antigenic determinants of γ-globulin revealed by pepsin digestion at pH 4.1. Sera containing such agglutinating activity as well as sera negative for these agglutinators contain low molecular weight (3S–5S) components of slow γ-mobility which inhibit these agglutination reactions. Low molecular weight inhibitors show both auto- and isospecificity, and are antigenically related to the 5S pepsin fragment of γ-globulin. A common situation is thereby revealed in which human anti-γ-globulin antibodies showing specificity for pepsin-digested γ-globulins are present in serum along with low molecular weight γ-globulin components capable of inhibition. Autoreactivity or autospecificity of such anti-γ-globulin factors is a phenomenon shared by both normal human sera and sera from patients with various disease states.

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