Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism

Study results suggest that the autoimmune targets in the Cunningham Panel™ can predict IVIG treatment response in a subset of autism patients.

Published: Translational Psychiatry
Case Reports in Psychiatry: Autoimmune targets in Cunningham Panel predict IVIG treatment response in subset of autism patients
In this study, the authors examined 82 children with “neurodevelopmental disorders for biomarkers consistent with [autoimmune encephalopathy] and considered for immunomodulatory treatment for those with a clinical presentation and laboratory values consistent with [autoimmune encephalopathy.]”

Of those who underwent IVIG treatment, the majority had symptom improvements.

Interestingly, “in our cohort of patients who presented to our ASD clinic, very few demonstrated autoantibodies usually associated with [autoimmune encephalopathy] in children.” For instance, none of the patients were positive for NMDA receptor or VGKC autoantibodies.

The Cunningham Panel™ of Tests predicted response to IVIG treatment with an accuracy of 81%, 88% and 88% on the ABC, SRS, and parental evaluations, respectively.

The majority of patients with autism spectrum disorder who had autoantibodies demonstrated elevations in autoantibodies measured by the Cunningham Panel™, along with an elevation in the activation of the CaMKII.

“Our analysis suggests that two of the autoantibodies, the anti-Tubulin and anti-D2R were associated with responsiveness to IVIG treatment,” the authors state, “suggesting that these could be biomarkers to select individuals who might benefit most from IVIG treatment.”


CASES HIGHLIGHTED IN THE STUDY

At 15 months old, a male patient had a sudden regression in speech, eye contact and fine motor skills. He underwent 6 years of speech and occupational therapy but could still only speak 3-4 word sentences.

He was not able to engage in reciprocal conversation and exhibited limited eye contact. He also suffered from severe restricted interests, anxiety, and had frequent meltdowns.

The child was treated for mitochondrial dysfunction with limited improvement in symptoms.

The Cunningham Panel™ was ordered, which showed elevations in anti-Tubulin antibodies (2000; nl = 250–1000) and in the CaMKII (151, nl < 130). The results prompted a trial of intravenous immunoglobulin (IVIG) at 1 g/kg/day × 2 days every month.

“Within 2 days of the IVIG treatment, his handwriting significantly improved.” And with each subsequent treatment, he progressively gained skills, including significant improvements in language.

After 5 months, he began having reciprocal conversations and was able to describe how IVIG made him “feel.” After 6 months, his restricted interests resolved.

After 18 months of IVIG treatment, the child had been able to sit with peers in a noisy gymnasium and engage within a small group in social conversation.

A young girl had been developing normally until approximately 3 years of age, at which point she began experiencing periodic episodes of “abrupt loss of previously acquired skills and developed other neuropsychiatric symptoms.”

At age 4, she developed a sudden onset of repetitive behaviors, tics, poor concentration, emotional liability, separation anxiety, urinary frequency and urgency, sleep disturbance, and aggressive behavior.

At age 8, she was diagnosed with autism spectrum disorder (ASD). One year later, she developed partial complex seizures, which were partially controlled with lamotrigine.

At age 7, the Cunningham Panel™ was ordered. Test results showed an elevated CaMKII (135; nl < 130) and she was treated with IVIG.

“Improvements occurred in tics, academics, and seizure frequency and the CaMKII normalized.”

However, the improvement wasn’t sustained and the child’s behavior quickly regressed. A repeat Cunningham Panel™ indicated the CaMKII was once again elevated and in the abnormal range.

After 6 months of treatment with monthly IVIG, her behavior improved.

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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.