Strep A: Recurrent Infections Affect The Brain

A group of researchers from Columbia University Medical Center and the University of Minnesota have discovered how recurrent infections of Strep A in children can trigger immune cells to enter the brain, which causes inflammation that can lead to autoimmune neuropsychiatric disorders.

The study was done on mice, finding that immune cells travel along odor-sensing neurons that emerge from the nasal cavity, instead of breaching the blood-brain barrier directly. The findings could help develop improved diagnostic, monitoring and treatment methods for these disorders.

Group A Strep, also known as Strep A or "Streptococcus Agalactiae," is a bacterium that causes many different infections, most notably strep throat and impetigo. Recurrent infections of strep have been linked to several autoimmune neuropsychiatric disorders, including PANDAS - Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections - which can happen overnight and immediately, and include OCD and other Tourettes-like "tic" disorders, according to the Mayo Clinic.

When a person gets Strep A, the immune system ends up producing autoanitobodies that attack the body's own tissues. Strep A's bacterial cell wall confuses the immune system because it contains mimetic molecules that are similar enough to those in the human heart, kidneys, and brain tissue, according to Dritan Agalliu, an assistant professor in the department of Pathology and Cell Biology at CUMC.

Scientists were previously unaware about how these autoantibodies gained access to the brain, since normally brain vessels form the tightly bound blood-brain barrier that does not allow free movement of molecules, antibodies, or immune cells into the brain from the blood.

However, recurrent Strep A infections can trigger the body to produce Th17 cells, an immune cell that's somewhat of a Helper T Cell, in the nasal cavity. The researchers found that in Strep A-infected mice, these bacterial-specific Th17 cells move on the surface of axons from the olfactory system into the olfactory bulb of the brain, the portion that processes odor information.

"Once the Th17 cells enter the brain, they break down the blood-brain barrier, allowing autoantibodies and other Th17 cells to enter the brain and promote neuroinflammation," Agalliu said in a press release. "What's interesting is that we see abundant Group A Strep bacteria in the nose, but they never penetrate the brain. This is different from Group B Strep - the cause of bacterial meningitis - which causes neuroinflammation by entering the brain directly."

This discovery is a huge step for developing a test for definitively diagnosing PANDAS, which can currently only be diagnosed based on clinical symptoms and the presence of Strep A, or autoantibodies against brain proteins.

"We are also interested in exploring ways to treat the disorder by repairing the blood-brain barrier itself to prevent the entry of autoantibodies into the brain," Agalliu said.

The findings were published in the Journal of Clinical Investigation.

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