Autoimmune Epilepsy - In Vivo Evidence from Animal Models That Patient’s IgGs Induce General Tonic-Clonic Seizures, Bind and Kill Neural Cells
Abstract number :
1.051
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2023
Submission ID :
65
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Rhoda Taiwo, PhD Candidate – THE HEBREW UNIVERSITY OF JERUSALEM
Hadassa Goldberg, Neurologist – Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel – Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Mia Levite, Prof. – Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Jerusalem – Faculty of Medicine, The Hebrew University, Ein Karem, Jerusalem 12065, Israel; Tawfeeq Shekh-Ahmad, Dr. – Senior Lecturer, Department of Pharmaceutics, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Ein Karem, Jerusalem 12065, Israel
Rationale:
Epilepsy affects ~50 million people. In ~30% of patients, the aetiology is unknown, and these patients become unresponsive to anti-epileptic drugs developing intractable epilepsy. Some of the intractable enigmatic cases of epilepsy are in fact due to Autoimmune Epilepsy. Autoimmune cause of epilepsy is suspected mainly in the presence of medically intractable seizures and at least one neural autoimmune antibody or inflammatory changes indicated in serum or spinal fluid. So far 14 different types of autoimmune antibodies have been detected in subpopulations of epilepsy patients, some of them already proven to cause substantial damage in vitro and in vivo. However, there was clear difference in specificities of synapse-reactive neural specific antibodies such as immunoglobulin G (IgG) and Glutamate receptor antibodies detected in patients with new-onset and chronic epilepsy with IgG representing ~75% of serum antibodies in humans and are the most common type of antibody found in blood circulation and extracellular fluids. We then ask, if purified IgG of few young patients that suffer for many years from recurrent and intractable epilepsy, induce of their own General Clonic Tonic (GTCS) seizures in normal rats.
Methods:
To test this, normal rats underwent double surgery and implantation: first of EEG recording electrodes, and second with osmotic minipumps pre-loaded with purified IgG of few epilepsy patients or of healthy controls. Then, the patient’s IgG was released continuously (24/7) from the minipumps and reached the brain, during one week. EEG was recorded and analyzed for seizure activity. At the end of the experiment, brains were removed and analyzed histologically for binding and brain damage caused by the patient’s IgG.
Results:
Our findings revealed that Patient’s purified IgG induced on its own seizures in 100% of the rats with an average seizure duration of 68 secs. The GTCS were most prominent in the first week and declined gradually in the coming three weeks. The patient’s IgG bound and killed neural cells in vivo in several brain regions while the IgG from healthy individual did so to a significantly lesser extent, if at all.
Conclusions:
IgG of young epilepsy patients with intractable epilepsy, cognitive deficits, and psychiatric impairments induce by itself seizures and brain damage in animal model in vivo.
Funding:
This research was supported by Israel Science Foundation and the U.S Department of Defense.
Basic Mechanisms