Dr. Madeleine Cunningham Autoimmunity and Behavior: Syndenham’s Chorea, PANDAS, and Related Disorders

Sydenham chorea is the major neurologic sequelae of group A streptococcal-induced acute rheumatic fever (ARF) and is most likely due to autoimmunity and molecular mimicry between host and pathogen. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) has also been suggested to be a sequelae of streptococcal infections. Human anti-streptococcal monoclonal antibodies(mAb) derived from Sydenham chorea targeted caudate putamen tissue as well as brain antigens lysoganglioside and tubulin. The chorea derived mAbs, acute Sydenham chorea sera and cerebrospinal fluid targeted human neuronal cells and signaled calcium-calmodulin dependent protein (CaM) kinase II activity and dopamine release in a neuronal cell line as well as in primary neuronal cells. New preliminary data suggest that dopamine D1 and D2 receptors may be targeted by the crossreactive anti-brain mAbs and sera. Serum antibodies from related disorders such as PANDAS with obsessive compulsive behaviors, vocal tics or tic-like movements demonstrated that the level of the CaM kinase II activity was increased along with antibodies against lysoganglioside and a number of neuronal antigens. Comparison of matched acute and convalescent PANDAS sera taken before and during the exacerbation demonstrated an elevation in CaM kinase II activity associated with disease. Study of an animal model of Sydenham chorea revealed that immunization with group A streptococcal antigen led to behavioral changes which correlated with antibody deposition in the striatum as well as reactivity of serum IgG with dopamine receptors and the induction of CaM kinase II activity. These data are consistent with the current hypothesis that central dopamine pathways may be involved in Sydenham chorea which is treated with haloperidol, a D2 receptor antagonist.

Madeleine Cunningham, PhD is a George Lynn Cross Research Professor, Department of Microbiology and Immunology, University of Oklahoma College of Medicine. Her research has focused on molecular mimicry, autoimmunity and infection. A focus of her laboratory includes the study of autoimmunity and behavior which is manifest in diseases such as Sydenham's chorea following group A streptococcal infection. Study identified antibody mediated neuronal cell signaling as the basis for the choreic movement disorder. Other related movement and psychiatric disorders such as obsessive compulsive disorder, Tourette's Syndrome and Tics are under investigation for subsets that may be related to streptococcal infection and/or to autoantibodies which signal in the brain. Dr. Cunningham's teaching focuses include microbial pathogenesis and immunology, host-parasite interactions, and bacterial pathogenesis, and medical and dental microbiology.

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