Therapeutic uses of gamma globulin

Abstract

Dr. Gold: In one of our conferences on therapy held in 1941 the topic of discussion was the use of human convalescent serum against infectious diseases. The object was to confer passive immunity for prophylaxis or for treatment in infectious diseases by the administration of antibodies obtained from humans. Human convalescent serum proved to be effective in prophylaxis against measles, in the prevention and cure of scarlet fever and there was some indication that it might be of value in mumps and whooping cough. There were serious obstacles in the way of the general development of this kind of therapy. The doses were large, the cost was high and human convalescent serum was available in only limited amounts and through special sources, as in the case of the Manhattan Convalescent Serum Laboratory which was affiliated with the Department of Health of New York City. This conference on the uses of gamma globulin is, in a sense, an extension of that subject in line with the developments which have taken place in the past few years. Dr. Edwin J. Cohn and his collaborators at Harvard Medical School devised a method for the large scale fractionation of plasma. It has been found that the protein fraction, termed “gamma globulin” in the form in which it was isolated, contains the major portion of the antibodies against infectious diseases. The solution of antibodies obtained from human plasma or serum has now become an article of commerce and is readily available at fairly reasonable cost. It is provided by several manufacturers in 2 cc. vials under the name of “immune serum globulin (human).” It represents an approximately 16 per cent solution of gamma globulin containing the antibodies present in normal pooled plasma but in a concentration about twenty-five times that of the original plasma. In the short period of time since the isolation of this material, its utility has been explored in a number of diseases: measles, scarlet fever, mumps, whooping cough, German measles, chicken pox, infantile diarrhea, poliomyelitis, serum hepatitis, infectious hepatitis and influenza. Thus far it has proved most effective in the prophylaxis of measles and infectious hepatitis. There is some indication that it may prevent homologous serum hepatitis and that large doses may act in a manner similar to convalescent serum in the prophylaxis or treatment of scarlet fever. The subject is still in the experimental stage. Evidence now exists indicating that some specific diseases in which gamma globulin prepared from normal pooled serum is not effective may respond to gamma globulin obtained from the plasma of patients convalescing from the disease. Thus, while the so-called “immune serum globulin (human)” has not been found effective in mumps, large doses of gamma globulin prepared from the plasma of convalescent patients have proved effective in preventing mumps orchitis, and gamma globulin prepared from the plasma of hyperimmunized donors has been found useful in the treatment and prevention of whooping cough. The use of gamma globulin in measles was discussed in some detail. The material now available is apparently without value after the disease is established and its use is restricted to prophylaxis. When the material is given at any time between the first and eighth day after exposure, it will either prevent measles or reduce measles to a very mild disease (modified measles) depending upon the size of the dose. The view was expressed that modification of measles is desirable in most cases since this apparently allows the patient to develop full immunity while passing through a very mild form of the disease, and that the prevention of the disease is desirable in only special cases as in very young infants and under other conditions in which an active measles would give rise to special hazards either to the individual or to contacts. The discussion also covered some of the details of administration and raised questions concerning the mode of action of gamma globulin. The current material is suitable only for intramuscular injection and is toxic by intravenous injection. The dose for complete prevention of measles is 0.2 cc. per Kg. and only about one-fourth of that, namely, 0.05 cc. per Kg. for the modification of measles. Local and systemic reactions occur in about 1 per cent of the cases and are usually mild. An interesting point concerning the mechanism of action was raised, namely, whether the results obtained with gamma globulin are due solely to the addition of antibodies to the patient's blood. There is some indication that the amount of antibodies so added may be too small to account for the protective effects and that some factor other than added antibodies may be, at least in part, responsible for the therapeutic results.