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Two examples of human IgM cold agglutinins agglutinated human RBC only after enzyme treatment in vitro. Proteases were optimally effective, neuraminidase was also effective. The cold agglutinins did not coat native RBC but were directed against "cryptic" RBC determinants. The cold agglutinins belonged to the anti -I/-i complex indicating a "new" type of I/i determinants. They were strongly accessible to cold agglutinin interaction on native RBC of a patient with congenital dyserythropoietic anaemia. Enzyme treatment of RBC was shown to be not only suited for defining cold agglutinin specificities but also essential for detecting the "new" type of cold agglutinins, obviously causing autoimmune haemolytic anaemia in vivo.
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