This blog is a way of sharing the information and resources that have helped me to recover my son Roo from an Autism Spectrum Disorder. What I have learned is to view our symptoms as the results of underlying biological cause, which can be identified and healed. I say "our symptoms" because I also have a neuro-immune disorder called Myalgic Encephalomyelitis.

And, of course, I am not a doctor (although I have been known to impersonate one while doing imaginative play with my son)- this is just our story and information that has been helpful or interesting to us. I hope it is helpful and interesting to you!

Wednesday, December 16, 2015

How the Auto Antibodies in PANDAS Get into the Brain

Linking intranasal group A Streptococcus infection to CNS complications 
(this is a video on the Journal of Clinical Investigation YouTube channel)

Recent research by Pat Cleary, Ph.D and Dritan Agalliu, Ph.D has shed light on some of the specific mechanisms by which group A strep infections can lead to PANDAS.  The question that struck them was how an infection (group A strep in this case) that doesn’t involve an infection of the brain, can result in the behavioral and motor changes seen in PANDAS? 

There are several known autoimmune complications that can follow strep infection, that typically show up 2 to 4 weeks after the infection.  These include Rheumatic Fever, Sydenham's Chorea, and PANDAS.  Dr Cunningham, another PANDAS researcher, has found autoantibodies in the blood of kids with PANDAS.  Cleary and Agalliu found that in mice, group A strep infections lead to a Th17 response.  Th17 cells are important in MS and are known to enter the brain.  They did experiments where they put strep A in the nose of mice several times, the mice become immune, and strep-specific T-cells were found in the mouse brains later.  These T-cells persisted for at least 50 days and could be activated to produce IL17 (a cytokine known to have an impact on the brain) simply by exposing the mice to strep in the nose.  These T-cells come from the mouse tonsils, where strep causes a major Th17 response.  Tonsils from children with PANDAS were also found to be loaded with Th17 cells. 

When they looked for where these strep-specific T-cells were in the brain, they were found in the olfactory bulb as well as all of the areas of the brain that the olfactory bulb sends information to, including the lateral hypothalamus and the amygdala.  The olfactory bulb receives information from the sensory neurons in the nose and transmits the information to the rest of the brain.  These findings suggest that the strep-specific Th17 cells enter the brain via the olfactory neurons and then use the pathways of the olfactory system to travel further into the brain.  It was also found that there were breaches in the blood-brain-barrier (BBB) in all of the brain regions where these T-cells were found.  Further investigation found that there were auto antibodies in the brain where ever the BBB had become breached.  These are antibodies to a protein on the strep bacteria that cross-reacts with a protein in the brain.  When they looked at what impact these autoantibodies might have on the function of the neurons in these regions, they found that excitatory glutaminergic synapses were decreased after multiple strep infections.  This is how Cleary summarizes the process:

“At some point when the T-cell numbers get to a particular level they migrate into the brain, and produce IL17 which opens up the BBB and allows IgG antibody, including auto antibody, to enter the brain.  Then, subsequent to the initial onslaught of T-cells into the brain, every time a child becomes exposed to strep those T-cells expand and you have an exacerbation of their behavior.”

You can read more about this here on the PANDAS Network website, and here from the Columbia University Medical Center.