46% of sera from 30 children with rheumatic chorea showed IgG antibody reacting with neuronal cytoplasm of human caudate and subthalamic nuclei. The antibody was also detected in 14% of 50 children with active rheumatic carditis. 55 normal control sera, as well as 148 sera from a broad variety of other disease states showed a low prevalence (1.8-4.0%) of positive reactions. In rheumatic chorea the presence of anti-neuronal antibody appeared to correlate with severity and duration of clinical attacks. Antibody reacting with neuronal cytoplasm was completely removed by absorption with Group A streptococcal membranes or with isolated human neurons from caudate nucleus. Partial absorption of antibody was also recorded using Group A cell wall preparations but not with Group A carbohydrate. No absorption of positive reactions was seen with streptococcal Group D membranes or cell walls. In rheumatic chorea, anti-neuronal antibody appeared to represent cross-reaction with antigens shared by Group A streptococcal membranes.

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Although the available evidence dearly indicates that the Group A streptococcus represents the probable etiological agent of acute rheumatic fever, its role in the pathogenesis of this disease remains obscure. One of the widely considered theories suggests that some individuals become sensitized to one or more streptococcal antigens during an infection with this microorganism, aad that the acute rheumatic process stems from the interaction between these antigens and antibodies within the tissues of the host. This concept of hypersensitivity has led to many studies of the antigens of Group A streptococci. However, in spite of the accumulation of a large body of information about these antigens, the pathogenesis of rheumatic fever remains an eni~na. No specific antigen has been identified, and the manner by which the inflammatory reaction is invoked and sustained is unknown at this time.In an attempt to determine whether**~treptococcal antigens or antigen-antibody complexes are present in the lesions of acute rheumatic fever, Coons reasoned that a visibly tagged antibody might be of aid in the localization of streptococcal antigens at the sites of histological damage in rheumatic fever (1). Although Coons turned from his original objective, the immunofluorescent technique which he developed has served as a spring board for many other investigations into the role of antigen-antibody reactions in rheumatic fever.In the early immunofluorescent studies, investigators examined the involvement of host gamma globulin in the pathological process. In a small series of patients, Vazquez and Dixon noted that gamma globulin was preferentially concentrated in the myocardial lesions of rheumatic fever (2). In a more extensive study by Kaplan, bound gamma globulin was detected in widely scattered sites throughout the myocardium in 20 % of a series of surgical specimens obtained from rheumatic hearts (3). In another detailed study, Wagner did not find any relationship between the bound gamma globulin which he demonstrated in the Aschoff bodies of rheumatic hearts and fluorescein-tagged streptococcal antigens. In addition, by using fluorescein-tagged Group A

Previous studies have shown that human serum containing anti-group A streptococcus carbohydrate (GAS CHO) antibodies were opsonic for different M protein-carrying serotypes. To investigate the role that anti-GAS CHO antibodies play in passive and active protection, mice were immunized subcutaneously or intranasally with GAS CHO conjugated to tetanus toxoid, and mortality and oral colonization were monitored after challenge with live GAS. Compared with control mice, immunized mice were significantly protected against systemic or nasal challenge with GAS. Furthermore, studies of serum samples and throat cultures from Mexican children revealed an inverse relationship between high serum titers of anti-GAS CHO antibodies and the presence of GAS in the throat. Anti-GAS CHO antibodies were also tested for cross-reactivity with human tissues and cytoskeletal proteins. No cross-reactivity was observed in either assay. The present study demonstrates that GAS CHO is both immunogenic and protective against GAS infections.Previous work from our laboratory has shown that serum samples from healthy children contain antibodies to group A streptococcus carbohydrate (GAS CHO) and that the titers of these antibodies increase with increasing age. These antibodies were also shown to be opsonic for several M protein-carrying (M+) serotypes of GAS in an in vitro phagocytic assay. In addition, the specificity of these antibodies for GAS CHO was clearly demonstrated, because removal of them by absorption with N-acetyl glucosamine coupled to Sepharose beads