Diclonal gammopathy in chronic cold agglutinin disease

Serum from a patient with chronic cold agglutinin disease (CCAD) contained two paraproteins identified as IgM kappa and IgM lambda by immunoelectrophoresis and confirmed by immunofixation on high resolution agarose gel electrophoresis. The IgM kappa band was completely removed by incubation of the serum at 4 degrees with ficin-treated O Rh-positive red blood cells, and partially removed by incubation with cord cells, suggesting that it reacted with I antigen. The IgM lambda band was unaffected by these absorptions. Previous investigators have shown CCAD to be a monoclonal gammopathy, usually IgM kappa. The presence of both IgM kappa and IgM lambda paraproteins in this patient with the IgM kappa showing cold agglutinin activity is unique. The patient has a lymphoplasmacytic infiltrate in the bone marrow. These data suggest that CCAD may be part of a spectrum of disorders in which paraproteins are produced and are stimulated by factors unrelated to the target red blood cell antigens.