A Preliminary Study of Heart and Brain Autoreactivity After Group A Streptococcal Carbohydrate Antigen Immunization in Rabbits ^†

There is current interest in the group A streptococcal carbohydrate as a vaccine antigen, and previous studies have suggested that it may induce host tissue cross-reactive autoantibodies which react with heart and brain autoantigens and which are present in streptococcal sequelae, including rheumatic heart disease, Sydenham chorea, and pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS). Rabbits were immunized with streptococcal carbohydrate antigens conjugated to tetanus toxoid carrier. Native group A carbohydrate (GAC) was prepared directly from wild type Streptococcus pyogenes (GAS) and variant GAC rhamnose was prepared from a GAS variant strain. Groups of eight rabbits were immunized with control vehicle and tetanus toxoid carriers alone, and GAC and variant GAC rhamnose antigens were conjugated to tetanus toxoid carrier proteins. Sera from immunized GAC and control rabbits was analyzed for IgG reactivity in the enzyme-linked immunosorbent assay against heart and brain antigens, including cardiac myosin, beta adrenergic receptors, muscarinic receptors, dopamine receptors, lysoganglioside, and tubulin. Heart and brain tissues (myocardium, valve, hippocampus, cortex, and basal ganglia) from immunized and control rabbits were analyzed for IgG deposition following immunization. Sera from GAC-immunized and control rabbits was analyzed for IgG binding to human heart and brain tissues, including myocardium, valve and basal ganglia. Sera from immunized rabbits did not demonstrate significant reactivity with any of the antigens and tissues above the background observed in tissues of vehicle and tetanus toxoid control animals. Studies of neuronal or heart cell signaling in protein kinase A (PKA) and calcium calmodulin dependent protein kinase II (CaMKII) signaling assays by sera were similar to controls.