The unitary nature of "complete" and "incomplete" pathologic cold hemagglutinins.

I T HAS BEEN well known for many years that the sera of patients with certam viral infections, acquired hemolytic anemia or other disorders may contam large quantities of proteins capable of directly agglutinating normal human erythrocytes during cold incubation.1’2 These proteins are designated pathologic “complete” cold agglutinins. The direct agglutination they produce is readily reversed by warming. The coexistence of pathologic “incomplete” cold antibodies was later inferred from the observation that red cells incubated with such cold agglutinating sera, after warming and washing, were no longer directly agglutinable in the cold but could be reagglutinated by an antiglobulin serum.35 The interpretation that these findings were indicative of a distinct “incomplete” antibody seems to have derived from an apparent analogy to the “incomplete” antibodies of human blood grouping systems, particularly the Rh system6 in which the existence of separate “complete” ( saline ) and “incomplete” agglutinins has now become firmly established.7’ Subsequent investigations5’”’12 have clearly shown that demonstration of the pathologic “incomplete” cold antibody activity, unlike direct cold aggl:mtination, requires the presence of fresh serum, presumably the complement ( C’) components, during the incubation. Furthermore, the reaction of antiglobulin sera with red cells sensitized by pathologic “incomplete” cold antibodies in the presence of fresh serum is not inhibited by prior addition of excess human yglobulin to the antiglobulin sera.5’ 14 This type of erythrocyte coating has therefore been designated “non-y-globulin” and is believed to represent, at least in part, bound C’ protein.11”2’14’6 The inccmplete cold antibody was presumed to be attached to the red cell surface in association with C’ components in such a manner that the antibody itself was unavailable to react with antisera to y-globulin.” The possibility that this form of incomplete antibody may not be y-globulin was also considered. ’14 Efforts to clarify this point have been hindered by inability to elute the coating proteins in a form permitting detailed ri47 More recently, on the other hand, Dacie, Crookston and Christenson postulated”2 that incomplete cold antibodies distinct from the complete cold agglutinins may not really exist; i.e., that the “non-y-globulin” erythrocyte coat-