UT Southwestern researchers recently reported that they had used cryoelectron microscopy to obtain the image of an auto-antibody that had bound itself to the surface receptor of a nerve cell. This discovery shows the mechanism behind neurological autoimmune illnesses and may be useful in the development of novel therapies for autoimmune diseases.
Autoimmune illnesses are disorders that cause an individual’s immune system to mistakenly attack their body. These illnesses reduce the body’s ability to fight germs such as viruses and bacteria, which in turn, makes individuals susceptible to infections. Common autoimmune illnesses include systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, psoriasis and type 1 diabetes.
The study, which was led by Ryan Hibbs and Colleen M. Noviello, was conducted after investigators in Germany identified an eight-year old patient with autoimmune encephalitis, which they believe was caused by antibodies attacking the γ-aminobutyric acid type A receptor (GABAA receptor). Autoimmune encephalitis is an inflammation in the brain that causes a person’s immune system to attack healthy tissues and cells in the spinal cord or brain.
Hibbs has specialized in biophysics and neuroscience and is a scientist at Charité – Universitätsmedizin Berlin, in the Harald Prüss lab; he is also a researcher in the Peter O’Donnell Jr. Brain Institute and an Effie Marie Cain scholar in medical research.
The researchers confirmed that two types of antibodies obtained from the immune cells of the patient bound to this particular receptor. Once this was done, the scientists, in collaboration with their partners in the Hibbs laboratory, carried out cryoelectron microscopy. The cryoelectron microscopy facility at UT Southwestern was launched about six years ago and offers three-dimensional images of biomacromolecules.
In their report, the researchers stated that autoantibodies that targeted neuronal membrane proteins caused seizures, encephalitis and acute behavioral abnormalities. They explained that while antibodies for a number of neuronal targets had been identified, scientists were in the dark on how they regulated function, until now.
Assistant professor of neuroscience at UT Southwestern, Noviello, who has specialized in capturing cryoelectron microscopy images up to atomic resolution, added that their findings ushered in a new era of understanding how autoimmune illnesses worked in the central nervous system. In their conclusion, they noted that they were now focused on identifying residues in the antibodies involved in affinity and specificity
The researchers and collaborators reported their findings in the “Cell” journal. They plan to partner with their colleagues to study more autoimmune illnesses that affect the human central nervous system.
Companies such as Aditxt Inc. (NASDAQ: ADTX) are also looking into mechanisms through which the immune system can be retrained so that autoimmune illnesses can be halted in their progression or even reversed so that patients can enjoy a better quality of life.
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