Background: Although it is known that IgM ĸ molecules predominate in cold agglutinins (CAs), exact data on the frequency of Ig classes and L-chain types (isotypes) of CAs and their distribution among CAs with different specificities are missing. Material and Methods:384 CAs of our collection were tested for isotypes by double diffusion or 2-mercaptoethanol treatment. CA specificities were determined using untreated, papain- and sialidase-treated red blood cells derived from human adults and newborns. Anti-Pr subspecificities were defined by chemically modified glycophorins and further characterized by specifically α2,3-desialylated red cells. Results: Almost all anti-I CAs are IgM. Almost all IgG and IgA examples are anti-Pr CAs, most of which are IgM. IgG and IgA CAs apparently accumulate within CAs with anti-Pr1h and anti-Pra subspecificities. λ-type IgM CAs are found among anti-I (6.5%) and anti-Pr CAs (8.7%) but are preferentially associated with anti-i CAs (20.6%). Conclusion: Ig class switching is rare in CAs. It is decisive for the mode and extent of red blood cell destruction. Autoimmune hemolysis due to IgM CAs is complement mediated. Red blood cell destruction induced by IgG CAs differs from that caused by IgM CAs, whereas IgA CAs do not cause (intense) immune hemolysis. CA class switching is associated with CA (sub)specificities. They reflect autoantigens capable of inducing class switching.

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1999
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