CD40LG and cold agglutinin disease: J-chain-negative, hexameric IgM has been shown to be a much more potent complement activator than regular IgM (20) and could therefore be of importance in the context of complement mediated disorders such as cold agglutinin disease (CAD), where monoclonal IgM leads to complement mediated hemolysis and erythrocyte agglutination (27–29).