Biologic Activity of Cold-Reacting Autoantibodies

IN 1832, Elliotson described a patient with heart disease and "cold fits" who passed bloody urine "whenever the east wind blew."1 Half a century later, Rosenbach described patients in whom hemoglobinuria occurred after their feet were immersed in ice water.2,3 In 1904, Donath and Landsteiner showed that in such patients an autolysin combined with red cells in the cold; lysis resulted from the action of labile serum factors (now known to be complement) when the temperature was subsequently raised.4In 1903, Landsteiner detected autoagglutination when blood from various mammalian species was chilled,5 but it was not until . . .