How Immune Response to Strep Infection Triggers BGE Breakdown of Blood–Brain Barrier
Research and awareness of PANDAS/PANS are essential to equipping providers with the best medical knowledge to support patients and their families. Recent findings unveiled crucial knowledge about the nature of autoimmune basal ganglia encephalitis.
New Columbia University research1 demonstrates how the immune response to strep throat triggers the blood–brain barrier breakdown in post-infectious basal ganglia encephalitis (BGE). These findings emphasize the need for early diagnosis and treatment to increase positive outcomes in children affected by PANDAS/PANS.
Strep throat causes the body to initiate an immune response against the infection. Certain patients produce antibodies, called auto-antibodies, that also attack the individual’s healthy brain cells. Previously, scientists did not have a strong understanding of how these autoantibodies entered the brain. These clinical findings provide crucial knowledge for expanding options for testing and managing your child’s PANDAS/PANS.
Autoimmune encephalitis (AE) is a group of central nervous system autoimmune disorders that occur when the body’s immune system mistakenly attacks healthy brain tissue. Post-infectious BGE is a subset of AE that results from bacterial, viral or fungal infections.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) are types of BGE associated with infection, most commonly strep.
The basal ganglia are a group of interconnected structures within the brain that regulate neural functions such as motor movement, cognitive and emotional response, and habit learning. Patients that have encephalitis of this basal ganglia region of the brain often have an abrupt onset of symptoms. Of course, certain children and adults may also be genetically susceptible to autoimmunity. This might explain why they develop BGE after an infection, while others do not.
Research generated from mouse models provides much-needed information about how the cells triggered in the immune response travel and damage the brain. This evidence will help improve diagnosing, treating and managing BGE disorders like PANDAS/PANS.
The blood–brain barrier is a highly selective, semi-permeable boundary of specialized cells—known as endothelial cells—that line the brain’s blood vessels. The blood–brain barrier protects the brain from infection by preventing molecules in the circulating blood from indiscriminately entering the brain.
Untreated strep throat in some patients leads to the production of these autoantibodies that may target the brain. These infections trigger a powerful cell response in areas of the body with bacteria to fight the infection. This typically happens in the nose, throat, and tonsils. Lymphocytes, or inflammatory cells, cause an inappropriate immune response that targets the patient’s healthy cells. Lymphocytes are commonly present in many autoimmune diseases.
Recurrent strep throat leads to the accumulation of lymphocytes in the mucous membrane, upper nasal cavity and surrounding tissue. Clinical research suggests that the cell response from T helper 17 (Th17) lymphocytes plays a critical role in transporting autoantibodies across the blood–brain barrier.
Recent studies in mice indicate that Th17 lymphocytes may travel along the odor-sensing olfactory nerves to the brain. Once in the brain, the lymphocytes release inflammatory cytokine proteins necessary for immune cell communication. The cytokines from the lymphocytes then stimulate specialized immune cells of the central nervous system, called microglia, to release more inflammatory cytokines. The inflammatory cytokines released by the lymphocytes and microglia cells trigger the breakdown of the blood–brain barrier, which allows toxins and pathogens to enter the brain.
Inflammatory cytokines released by Th17 lymphocytes and microglia cells trigger the breakdown of the blood–brain barrier by:
- Damaging tight junction (TJ) proteins. TJ proteins join endothelial cells of the blood–brain barrier to prevent the transport of molecules from the blood to the brain.
- Increasing endothelial transcytosis, or the transport of molecules. In endothelial transcytosis, molecules are transported within endothelial cells and into the brain.
This combination of factors allows autoantibodies circulating in the blood to enter the brain, where they can cause damage. Findings from this research are crucial for improving the knowledge base on PANDAS/PAN and other BGE disorders for providers and families.
Children with PANDAS/PANS often present with behavioral and neurological symptoms. The immune cell response from untreated strep throat can result in these types of symptoms.
Studies in mice indicate that the Th17 lymphocytes are essential in transporting autoantibodies across the blood–brain barrier. Once the lymphocytes enter the brain, they begin to interfere with neuronal function. This process can lead to the abrupt onset of neurological and psychiatric symptoms associated with PANDAS/PAN and other BGE disorders.
These new findings on the effects of strep throat identify the role of Th17 lymphocytes in the breakdown of the blood–brain barrier. Groundbreaking research is currently underway to examine the role of these lymphocytes in humans suffering from post-infectious BGE disorders. In time, results from human studies may increase options for the diagnosis of children with PANDAS/PANS.
There is no definitive test for PANDAS/PANS. Currently, these disorders are diagnosed based on clinical symptoms and the presence of strep A infection or autoantibodies against cytokine proteins in the brain. Understanding how to stop and treat the breakdown of the blood–brain barrier is essential to providing better support and care to families affected by these diseases.
Early identification of BGE cases is critical to improving treatment and management in patients. For children living with PANDAS/PANS, early treatment is certainly key to reducing permanent complications from the disease.
Families struggling with the impact of PANDAS/PANS can find resources on our website. You can also receive support and guidance from their communities. For example, you can connect with other parents and children affected by this disease by joining a local support group. You can also learn from other families’ experiences and get to know more about diagnostic and treatment options in your area. Peer support groups are active in the United States and internationally.
Our knowledge of PANDAS/PANS is constantly advancing with new diagnostic and treatment options, and more research to better understand these disorders. Stay up-to-date on the latest PANDAS/PAN research on our website.
- Columbia University Irvine Medical Center. 2015. “How Recurrent Strep A Infections Affect the Brain.” News. https://www.cuimc.columbia.edu/news/how-recurrent-strep-infections-affect-brain.