Cold agglutinin disease Cold agglutinin disease (cold antibody disease) is caused by autoantibodies that react at temperatures < 37 ° C Causes include Idiopathic (usually associated with a clonal B-cell population) Infections, especially mycoplasmal pneumonias or infectious mononucleosis (antibodies are directed against the I [mycoplasma] or i [Epstein Barr virus] antigens) Lymphoproliferative disorders (antibodies are usually directed against the I antigen) Infections tend to cause acute disease, whereas idiopathic disease (the common form in older adults) tends to be chronic.