Cold agglutinin isotypes

Background: Although it is known that IgM kappa molecules predominate in co ld agglutinins (CAs), exact data on the frequency of Ig classes and L-chain types (isotypes) of CAs and their distribution among CAs with different sp ecificities are missing. Material and Methods: 384 CAs of our collection we re tested for isotypes by double diffusion or 2-mercaptoethanol treatment. CA specificities were determined using untreated, papain- and sialidase-tre ated red blood cells derived from human adults and newborns. Anti-Pr subspe cificities were defined by chemically modified glycophorins and further cha racterized by specifically alpha 2,3-desialylated red cells. Results: Almos t 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 wit h anti-Pr-1h and anti-Pr-a subspecificities. lambda-type IgM CAs are found among anti-I (6.5%) and anti-Pr CAs (8.7%) but are preferentially associate d with anti-i CAs (20.6%). Conclusion: Ig class switching is rare in CAs. I t is decisive for the mode and extent of red blood cell destruction. Autoim mune hemolysis due to IgM CAs is complement mediated. Red blood cell destru ction induced by IgG CAs differs from that caused by IgM CAs, whereas IgA C As do not cause (intense) immune hemolysis. CA class switching is associate d with CA (sub)specificities. They reflect autoantigens capable of inducing class switching.