Serologic Response to Streptococcal Hemolysin and Hyaluronidase in Streptococcal and Rheumatic Infection.

Although it has as yet not been possible to demonstrate the specific role of a causative organism in rheumatic fever, there has been considerable epidemiologic (1) and serologic (2) evidence of some relationship between the hemolytic streptococcus and this disease. Studies of both cellular and extracellular substances of the hemolytic streptococcus have with rare exceptions shown that groups of patients with acute rheumatic fever were indistinguishable, by serologic reactions, from streptococcal convalescents. These studies have included those of reactions to cellular antigens, such as agglutination, precipitation with the M protein, and, more recently, complement fixation with somatic nucleoprotein fractions (3, 4); and, among the reactions to extracellular antigens, antistreptolysin, antifibrinolysin, and, most recently, antihyaluronidase. A number of reports have shown that the sera of patients with acute rheumatic fever contained antibodies to streptococcal hyaluronidase in equal or greater concentration than those of patients convalescing from acute infection with the hemolytic streptococcus (5-10). This difference was manifest in both a higher geometric mean titer among the rheumatic fever patients and by a distribution of these titers which extended beyond the range of antihyaluronidase titers found after acute streptococcal infection. (The antihyaluronidase referred to here is the neutralizing antibody specific for hyaluronidase of streptococcal origin, and is stable at 560 C. for 30 minutes. This point is made because in addition to the one or more thermolabile inhibitors of testicular hyaluronidase which have been described in human sera [11-14], thermolabile inhibitors of streptococcal hyaluronidase have been described which can be reactivated by complement [15, 16]. The latter are distinct from the specific, thermostable inhibitor which has been measured in these studies.) This difference between the antihyaluronidase titers in rheumatic and streptococcal infection has been discussed elsewhere (7). First, the factor of time was considered as a possible cause for this difference, since the streptococcal convalescents included in our series were studied three weeks after the onset of the disease, and it was felt that perhaps the longer contact with the streptococcus which some of the rheumatic patients may have had might have given rise to a greater production of this antibody. Other serologic circumstances which might give rise to such a difference were considered. Finally it was pointed out that only after thorough exploration of such possibilities could the question be raised as to whether the relatively higher antihyaluronidase titers in rheumatic fever might have any implication of some role of streptococcal hyaluronidase in the pathogenesis of this disease. The current study was undertaken in an attempt to explore further the relationships of antihyaluronidase to scarlet fever and rheumatic fever, and where possible to compare it directly with the titers of antistreptolysin, in an effort to detect any possible relationship of antihyaluronidase to rheu'matic fever and scarlet fever which was different from that of the more widely studied antistreptolysin. For this purpose an effort was made this year to collect as many more sets of sera as possible from patients with scarlet fever at the onset of symptoms or shortly thereafter, three weeks later, and again six weeks later. Similarly, sera were collected from presumably normal subjects of the same age group, and also from patients with definite acute rheumatic fever in the same period of time. These were studied for comparison. It was felt, in view of the widespread presence of the hemolytic streptococcus, and the variations which may be encountered from year to year in