Agglutinins for various artificially altered red blood cells belong to the class of 19S macroglobulins, which migrate electrophoretically as fast gamma or slow beta globulins. The agglutinin activity of serum for altered red cells is readily destroyed by sulfhydryl compounds. Hemolysins for altered red cells are not readily recoverable from serum fractions prepared by starch block electrophoresis or density gradient ultracentrifugation, but, when present, are found to have the same properties. This information lends credence to the concept of these serum factors as examples of "natural antibody," although the stimulus to their formation is not understood.

The sera from patients with various types of hemolytic anemias and various dysproteinemias including macroglobulinemia were found to contain normal amounts of altered red cell agglutinins and hemolysins.

The sera from three patients with congenital agammaglobulinemia were studied. Two of these sera contained agglutinins and hemolysins for altered red blood cells, as well as isohemolysins and isoagglutinins. The significance of this finding is discussed.

The "T" agglutinin and the agglutinin for periodate-treated red cells, both of which are macroglobulins, have been shown by other workers to be absent from newborn sera. Their inability to cross the placenta can be explained by their large size.

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