New Research On PANDAS: Strep pharynx, PANDAS and molecular mimicry
December 15, 2015
Researchers be in possession of discovered how immune cells triggered ~ means of recurrent Strep A infections enter the brain, causing violence that may lead to autoimmune neuropsychiatric disorders in children. The study, performed in mice, base that immune cells reach the brain by traveling along odor-sensing neurons that come forth from the nasal cavity, not ~ dint of. breaching the blood–brain barrier without circumlocution. The findings could lead to improved methods as far as concerns diagnosing, monitoring, and treating these disorders.
The study, led ~ dint of. researchers at Columbia University Medical Center (CUMC) and the University of Minnesota, Minneapolis, was published today in the online impression of the Journal of Clinical Investigation.
Recurrent Group A streptococcus (S. pyogenes) infections, what one. cause “strep throat,” be obliged been linked to autoimmune neuropsychiatric disorders, notably Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections, or PANDAS. Children through PANDAS exhibit Tourette’s syndrome–like motor and vocal tics or obsessive-compulsive behaviors that look to happen “out of the pallid.”
The Strep A bacterial enclosed space wall contains molecules similar to those construct in human heart, kidney, or brain conglomeration, according to a co-leader of the study, Dritan Agalliu, PhD, ally professor of pathology and cell biology (in neurology and pharmacology) at Columbia University Medical Center. These “mimetic” molecules are recognized by the immune system, which responds ~ means of producing protective antibodies. But because of this corpuscular mimicry, the antibodies react not simply to the bacteria but also to the throng tissues, producing autoantibodies that attack the body’s acknowledge tissues. Previously, scientists did not conceive how these autoantibodies would gain entrance to the brain, because brain vessels form some extremely tight blood–brain barrier that prevents unrestrained movement of molecules, antibodies and immune cells from the disposition into the brain.
A few years ~ne, researchers discovered that recurrent Strep A infections trigger the work of immune cells known as Th17 cells, a original of helper T cell, in the nasal cavity. But it was unclear how these Th17 cells be in advance of to brain inflammation and symptoms such as those seen in children by PANDAS.
Studying the tissues of mice infected intranasally through Strep A, Drs. Agalliu and colleagues raise that bacterial-specific Th17 cells impel along the surface of olfactory, or odor-sensing, axons that extend from the nasal empty space through the cribriform plate, a sieve-like bone that separates the nasal void from the brain. From there, the cells extend to the olfactory bulb in the brain, what one. processes information about odors.
“Once the Th17 cells register the brain, they break down the vital fluid–brain barrier, allowing autoantibodies and other Th17 cells to enroll the brain and promote neuroinflammation,” related Dr. Agalliu. “What’s attractive is that we see abundant Group A Strep bacteria in the nose, if it were not that they never penetrate the brain,” he added. “This is many from Group B Strep—the spring of bacterial meningitis—which causes neuroinflammation through entering the brain directly.”
The findings may lead to a more determinate diagnostic test for PANDAS, which is currently diagnosed based on clinical symptoms and the state-room of Strep A infection or autoantibodies in requital for brain proteins. “We are furthermore interested in exploring ways to behave to the disorder by repairing the life-~–brain barrier itself to prevent the inlet of autoantibodies into the brain,” uttered Dr. Agalliu.
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