Researchers at the Lankenau Institute for Medical Research (LIMR) have created a simple diagnostic test for an autoimmune disorder that can lead to serious psychiatric symptoms. As part of their work, they isolated and cloned auto-antibodies that may help elucidate the underlying cellular mechanisms of the disease, which is a kind of brain inflammation depicted in the 2016 docudrama “Brain on Fire.”
Rashmi Sharma, PhD (pictured left), postdoctoral fellow, and Fetweh Al-Saleem, PhD (right), research assistant professor, both of whom work in the lab of LIMR Professor Scott Dessain, MD, PhD (center), were first authors on two recently published studies describing this work.
This inflammatory brain condition, referred to medically as anti-NMDA receptor encephalitis (ANRE), occurs when the body’s immune system attacks brain cells. ANRE can lead to seizures, hallucinations, confusion, memory loss, uncontrollable body movements, and can even be fatal. About 30 percent of patients are children and teenagers, and females are affected more often than males, according to the Encephalitis Society. ANRE can be cured if it is identified early and appropriately treated, but the only currently available diagnostic test cannot be performed in most clinical laboratories.
To address this issue, Dr. Dessain and his team created a simple ANRE assay that can be adapted for use with common clinical laboratory techniques. Their results were published recently in a research report entitled “Membrane-bound and soluble forms of an NMDA receptor extracellular domain retain epitopes targeted in auto-immune encephalitis” in the journal BMC Biotechnology.
“Our discovery will help doctors to more easily identify patients who have this treatable neurological and psychiatric disease,” said Dr. Dessain, the Joseph and Ray Gordon Chair in Clinical Oncology and Research.
In a companion study, members of this research group demonstrated their ability to isolate and clone, or replicate, NMDA receptor auto-antibodies from an 18-year-old female patient who had been diagnosed with ANRE. Results of that study, “Monoclonal antibodies from a patient with anti-NMDA receptor encephalitis,” were published recently in the Annals of Clinical and Translational Neurology.
“Our ability to isolate and then replicate the auto-antibodies from this patient offers researchers an unprecedented opportunity to explore the mechanisms that underlie ANRE,” said Dr. Sharma. “These auto-antibodies also provide standards for the diagnostic test we described in our first study.”
LIMR Professor Robert Cox, PhD, was a coauthor on the companion study. The LIMR team worked with David R. Lynch, MD, PhD, and other researchers from the Children’s Hospital of Philadelphia, as well as collaborators at the University of Texas at Austin and the Universidade Federal de Minas Gerais in Brazil.
Both studies were supported by a grant from the National Institutes of Health.