Autoantibody biomarkers for basal ganglia encephalitis in Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections

Published: Frontiers in Psychiatry

Author’s Remarks: Dr. Madeleine Cunningham

Dr. Madeleine Cunningham, co-author, reviews the utilization of antineuronal antibodies (measured with the Cunningham Panel™) as biomarkers for infection-triggered, autoimmune, basal ganglia encephalitis and the significance of the CaMKinase II.

The last paper that was published, which is just a few days ago, explains these antineuronal antibodies or biomarkers in basal ganglia encephalitis and it's taken 20 years of work for us to get to the point that we felt comfortable saying that Sydenham’s chorea and PANDAS were a type of basal ganglia encephalitis.

This group of four autoantibodies and their functional signaling assay [CaMKinase II] (which comprise the Cunningham Panel) actually detect basal ganglia encephalitis in children.

These antibodies go directly to the basal ganglia in animal models where we actually express the genes for these antibodies from humans in mice. They go straight to the basal ganglia and attack neurons. Neurons bind the antibodies and become full of the antibodies. So, the neurons are not able to function in these diseases.

One of the important findings from our study was that as we began to look at the data, and we began to realize that all of our normal controls had no CaMKinase activation in their assays.  When you place the normal sera on the human neuronal cells, there is no activation above baseline or above basal levels in the normals. But in the disease, you can see very readily that the CaMKinase is activated. 

Everyone may be wondering, “What's the importance of the CaMKinase?” This long named molecule -  the calcium calmodulin-dependent protein kinase 2.

It’s just a mouthful but this molecule is really important because it actually leads to tyrosine hydroxylase, which is the hallmark of all dopaminergic neurons and that enzyme leads to the production of dopamine and the release of dopamine eventually occurs.

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B. Robert Mozayeni, MD

Medical and Clinical Advisor

B. Robert Mozayeni MD

Dr. B. Robert Mozayeni was trained in Internal Medicine and Rheumatology at Yale and at NIH. He has had pre- and post-doctoral Fellowships in Molecular Biophysics and Biochemistry at Yale, and also at NIH where he was a Howard Hughes Research Scholar at LMB/DCBD/NCI and later, Senior Staff Fellow at LMMB/NHLBI/NIH. Editorial board of Infectious Diseases – Surveillance, Prevention and Treatment. Past President of the International Lyme and Associated Diseases Society (ILADS).

He is an expert in Translational Medicine, the science and art of advancing medical science safely and efficiently. He is a Fellow of the non-profit Think Lead Innovate Foundation and is a co-founder of the Foundation for the Study of Inflammatory Diseases. He is a Founder of the Foundation for the Study of Inflammatory Diseases to crowd-source medical solutions for complex conditions using existing knowledge, diagnostic methods, and therapies to meet patient needs immediately. He is the Chief Medical Officer of Galaxy Diagnostics, LLC. He is a Board member of the Human-Kind Alliance. Dr. Mozayeni has held admitting privileges (since 1994) on the clinical staff of Suburban Hospital, a member of Johns Hopkins Medicine and an affiliate of the National Institutes of Health Clinical Center.

Safedin Sajo Beqaj, PhD, HCLD, CC (ABB)

Moleculera Labs, Clinical Laboratory Advisor
Medical Database, Inc., President and CEO

Sajo Baqaj, PhD

Dr. Sajo Beqaj is board certified in molecular pathology and genetics and licensed as a Bioanalyst and High Complexity Laboratory Director. He has been practicing as a laboratory director since 2005.

Dr. Beqaj served as a technical director and was part of the initial management team for several well-known laboratories in the clinical lab industry including PathGroup, Nashville, TN; DCL Medical Laboratories, Indianapolis, IN, and Pathology, Inc, Torrance, CA. He is currently serving as off-side CLIA laboratory director for BioCorp Clinical Laboratory, Whittier, CA and Health360 Labs, Garden Grove, CA.

Dr. Beqaj received his Ph.D. in Pathology from Wayne State University Medical School, Detroit, Michigan. He performed his post-doctoral fellowship at Abbott Laboratories from 2001-2003 and with Children’s Hospital and Northwestern University from 2003-2005.

Dr. Beqaj has taught in several academic institutions and has published numerous medical textbook chapters and journal articles. He has served as a principal investigator in clinical trials for several well-known pharmaceutical and diagnostic companies such as Roche HPV Athena, Merck HPV vaccine, BD vaginitis panel, Roche (Vantana) CINtec® Histology clinical trials, and has presented various scientific clinical abstracts and presentations.

He is a member of several medical and scientific associations including the Association of Molecular Pathology, American Association of Clinical Chemistry and the Pan Am Society for Clinical Virology. He has served on a number of clinical laboratory regulatory and scientific committees, and has assisted several laboratories and physicians as a Clinical Laboratory Consultant.