FREE ANTIGEN AND ANTIBODY CIRCULATING TOGETHER IN LARGE AMOUNTS (HEMAGGLUTININ AND AGGLUTINOGEN IN THE BLOOD OF TRANSFUSED RABBITS)

In rabbits transfused almost daily with the whole citrated blood of other rabbits, an extraordinary condition often develops, which manifests itself in an almost immediate clumping together of all the red cells in specimens of the shed blood. This clumping is due to one or more true agglutinins, of which the strength may be such as to cause clumping in a 1: 2,800 plasma dilution. The agglutinating principle circulates with the corpuscles against which it is effective; but under ordinary circumstances intravascular clumping fails to occur because the union of antigen and antibody can take place only at a temperature several degrees below that of the body. If the temperature is sufficiently lowered, as when a tourniquet is applied to the rabbit's ear, intravascular clumping ensues. In defibrinated blood, gradually cooled, clumping is first noted as the temperature of 35°C. is approached; and at room temperature (22°) the corpuscles will often come together in a short time into a single, solid mass. At 0°C. the agglutination is still more marked. The reaction seems to be completely reversible, for when the blood is warmed again, the clumps break up and disappear at between 35° and 36°C. Cooling and warming with the resultant clumping and dissociation can be carried out many times on the same blood specimen without apparent change in the corpuscles or in the rapidity of the reaction. The response to temperature changes is extremely prompt. Once it has been elicited, the agglutinating principle may persist for a long time after the transfusions are stopped, in one instance it was still strong 133 days after the last transfusion. During this period the plethora was succeeded by a severe anemia, which in turn was recovered from. In many rabbits no agglutinin develops, and a continuance of the transfusions will not elicit it. Indeed, when present it tends to disappear if the transfusions are persisted in. In several of the animals in which the agglutinin was strongest, the plethora was suddenly succeeded by severe anemia, despite continued transfusions. The character of the temperature control of the agglutination, which somewhat resembles that of the hemolysin in paroxysmal hemoglobinuria, has led us to consider whether the blood destruction might not be due to accidental chilling of the animal. Efforts to induce a fall in the hemoglobin by placing the rabbit's ear in ice water have as yet been unsuccessful. Thus far no adequate search for an hemolysin has been made. The object of the present paper has been to describe a condition in which large amounts of free antigen and antibody circulate together in the organism, and to demonstrate the factor which prevents their union, the results of which could easily be fatal. The causes of the condition will be dealt with in a subsequent communication.