Acute phase haemolysis in chronic cold agglutinin disease

We previously described a paradoxical form of chronic cold agglutinin disea se (CAD) in which haemolysis occurred during episodes of fever but only mar ginally during exposure to colds. In order to investigate the molecular bas is for this response we performed a 12-month prospective study of a patient with CAD and paradoxical haemolysis. Blood samples were collected monthly during health, and daily following hospitalization owing to hip fracture. D uring health we observed decreased levels of C3, undetectable C4, a non-fun ctional classical pathway and a normal alternative pathway. Increased conce ntrations of C1-INH/Clrs complexes indicated continuous formation of C1-ant ibody-antigen complexes. There was a low-grade temperature-dependent fluctu ating haemolysis as evidenced from measurements of lactate dehydrogenase. F ollowing the hip fracture, the haemolysis increased. Levels of interleukin (IL)-1 beta, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF)- alpha increased as did C1-INH, C3, C4, CRP, and lactate dehydrogenase. The results support our hypothesis stating that paradoxical haemolysis in CAD i s controlled by the availability of early classical pathway complement mole cules and that haemolysis following acute phase responses occurs as a conse quence of increased complement synthesis.