Madeleine W. Cunningham, Ph.D.
George Lynn Cross Research Professor
Presbyterian Health Foundation Presidential Professor
Microbiology and Immunology
Director, Immunology Training Program
University of Oklahoma Health Sciences Center
Biomedical Research Center
Oklahoma City, OK
From Bench to Bedside: Anti-Neuronal Autoantibodies in Lyme Disease and Beyond
Dr Madeleine Cunningham has investigated the molecular pathogenesis of rheumatic fever and its sequelae for the past 30+ years, including rheumatic heart disease and Sydenham chorea. Currently, her laboratory is supported by the National Heart Lung and Blood Institute to investigate myocarditis and heart failure. She has also been supported by the National Institute
for Mental Health for her studies in pediatric acute onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Others have supported her work to investigate a group of anti-neuronal autoantibodies associated with Sydenham chorea and PANDAS/PANS to determine if the autoantibodies are present and are potential contributors to neurological impairment in other infectious sequelae such as Lyme disease and Post Treatment Lyme Disease Syndrome. The Lyme Disease Association provided funding for the first study of Lyme Disease and the group of anti-neuronal autoantibodies which are believed to represent a group of autoantibodies which
target the basal ganglia and may lead to mild to severe encephalitis. Most recently, the GlobalLyme Alliance supported studies of anti-neuronal autoantibodies in a Lyme Disease cohort. Dr. Cunningham co-founded Moleculera Labs in the University of Oklahoma Health Sciences Center Research Park and continues to serve as consultant and chief scientific officer and perform
research in her laboratory at the University of Oklahoma Health Sciences Center campus on the immune mechanisms in PANDAS/PANS including Lyme Disease and its sequelae. Dr. Cunningham received her PhD at the University of Tennessee Center for the Health Sciences in Memphis, TN, training under Drs Edwin Beachey and Gene Stollerman. She was a postdoctoral fellow at the Oklahoma Medical Research Foundation(OMRF) in Oklahoma City trained by Dr. Jordan Tang and then continued her research in streptococcal diseases and sequelae at the University of Oklahoma Health Sciences Center (OUHSC) where she is currently a George Lynn Cross Research Professor, Presbyterian Health Foundation Presidential Professor and Director of the OUHSC/OMRF T32 training program supported for the past nearly 20 years by the National Institute of Allergy and Immunology Diseases(NIAID).
Conference Lecture Summary
Molecular mimicry targeting neural tissue has been reported after Borrelia burgdorferi (Bb) infection, and antibody crossreactivity with group A streptococci has been previously suggested in Bb animal models. In this presentation, I will review the results from two recent studies in which we have investigated whether adults with Lyme disease(LD) have an elevation in a group of antineuronal autoantibodies previously found to be elevated in streptococcal infections and persist in Sydenham chorea, the neurologic manifestation of acute rheumatic fever. We have also used a functional assay to examine whether serum from prior LD with erythema migrans signaled a human neuronal cell line (as measured by the activation of calcium calmodulin dependent protein kinase II (CaMKII)). Our studies were conducted among patients with erythema migrans, convalescent erythema migrans, post-treatment Lyme disease, and non-Bb-infected controls. The results of two studies will be reported – one from the Center at Columbia University and other from the Center at Johns Hopkins College of Medicine.