The facts that an individual may produce antibodies against his own red blood cells and that such hemolyzing and agglutinating antibodies may be responsible for hemolytic anemia have been known since the beginning of the century. Donath and Landsteiner described in 1904 hemolysins for the patient's own red cells in paroxysmal cold hemoglobinuria. Soon afterward, Widal, Abrami and Brul6,' Chauffard and Troisier, and Chauffard and Vincent incriminated so-called auto-antibodies for some hemolytic anemias. A review of the literature during 30 years following the significant observations of the French investigators reveals only occasional reports on the role of auto-antibodies in hemolytic anemia. The difficulty in demonstrating these antibodies seems to have been the reason. The subject remained dormant until Dameshek and Schwartz revived it by their ingenious experimental studies. They produced hemolytic anemia in guinea pigs with a rabbit immune serum containing hemolytic antibodies against guinea-pig red cells. From these results and from clinical observations, Dameshek and Schwartz postulated the responsibility of an antigen-antibody reaction for certain forms of hemolytic anemia in man. The next important event was the discovery in the middle forties by workers in the Rh field of so-called incomplete antibodies capable of reacting demonstrably only in a favorable environment, provided by a suitable diluent and temperature of incubation. Clumping of red cells becomes manifest in the presence of large molecular diluents (albumin, serum, certain synthetic compounds such as dextran and polyvinylpyrrolidone), but not when one employs physiologic solution of sodium chloride, the time-honored reagent for dilution of antibody containing serum and for suspension of red blood cells. Most significant for the study of auto-antibodies in hemolytic anemia was the introduction by Coombs of the antiglobulin test, the principle of which was discovered by Friedberger and Moreschi.' Another step forward was the demonstration of increased sensitiveness of test red blood cells treated with proteolytic enzymes (trypsin, papain, etc.). The various methods for detection of auto-antibodies are listed in Table 1.
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