Group a Hemolytic Streptococcus Antibodies. I. Griffith Type Agglutinin and Antistreptolysin Titers in Normal Men and in Acute Infections.

The immunological phenomena associated with various aspects of hemolytic streptococcus disease in man have usually been studied by the measurement of antitoxins. Most extensive have been the observations made by the Dick technique (1), in which purified erythrogenic toxin was used as a skin test material. Circulating antistreptolysin and antifibrinolysin titers have also been determined, particularly in individuals suffering from glomerulonephritis and rheumatic fever (2). The measurement of antibacterial antibodies has been less satisfactory. Phagocytosis (3) and the destruction of the living organism by whole blood (4) have been the most recent methods of choice. The agglutination of hemolytic streptococci by human serum has also been frequently studied (5). Many attempts were made during the first two decades of this century to establish the etiological relationship between streptococci and scarlet fever and many other diseases by the application of agglutination tests, using as antigens streptococci isolated from various sources. Usually, it was demonstrated that the convalescent serum of individuals suffering from infectious processes, now known to be caused by the hemolytic streptococcus, had higher titers of agglutinins than had controls, but the difficulties inherent in the production of stable antigens and the many confusing cross reactions caused a nearly complete abandonment of the phenomenon of agglutination as a means of study of streptococcus disease. Much more recently several studies have been made of the hemolytic streptococcus agglutinin content of the sera of individuals suffering from various forms of arthritis, which have indicated that increased amounts of these antibodies are present in association with the rheumatoid type (6). The variations from the normal have not been sufficiently great to permit the use of the agglutination test in the diagnosis of disease of the joints, nor to establish definitely the role of the streptococcus in the causation of rheumatoid arthritis. One group has described the agglutination of hemolytic streptococci by high dilutions of serum obtained from febrile patients known not to be suffering from streptococcus infections (7). It has been recently demonstrated that nearly all serious human infections, particularly those involving the respiratory passages, are caused by hemolytic streptococci serologically homogenous, the members of the Lancefield Group A (8). By the application of a technique of slide agglutination, more than 20 types have been identified within this group (9). Antibacterial immunity to infection with organisms of Group A, like that of the pneumococci, has been shown to be largely type specific (10). It is apparent, therefore, that the satisfactory study of the agglutinin content of human sera for the hemolytic streptococci pathogenic for man must be conducted in such a way that antigens made from strains of many types may be used. This can easily be accomplished by the application of a slide technique, first described by Ozaki (11), who, using antigens of all of the Griffith types, found that each was agglutinated by a small number of normal sera. Later, other Japanese workers (12) studied acute and convalescent sera obtained from individuals ill with scarlet fever. They also demonstrated that agglutinins for many types were present and that 39 per cent showed a definite increase in the amount of antibody for the homologous type of streptococcus during convalescence. Walker (13) also studied the development of agglutinins in scarlet fever by the slide method and showed that these antibodies appeared in approximately 25 per cent of all cases and-that they were type specific.