Friday 2 June 2017

Pandas

I mentioned scarlet fever in passing as the cause of deafness for Annie Jump Cannon, arguably the most formidable women in the history of astronomy. She was born in 1863 and for another 80 years scarlatina continued to be a major cause of mortality among children in the Western World. About 100 years ago, they tried to develop a vaccine - so effective against smallpox - but largely to no avail. The causative organism group A streptococcus (GAS) notably Streptococcus pyogenes is notorious for its shape-changing ability to evade our immune system. I don't mean literally shape-changing because S. pyogenes is a gram-positive coccus that goes in characteristic strings [R above stained blue from the Gram-stain].

Knocking scarlet fever on the head was one of the early triumphs of penicillin in the 1940s. In those days, when doctors still made house-calls, he [then almost always a he] would ask the ailing child to stick out the tongue. The diagnosis was confirmed if a 'strawberry tongue' [R] was presented. Normally S.pyogenesis is fairly innocuous. When it becomes infected with a T12 virus, however, it switches on the speA gene to produce Streptococcal pyrogenic exotoxin A and this protein is what causes systemic damage to the throat, skin and mind of the human host. If you survive, you will be immune to further infections from similar bugs. But you may, like Annie Jump Cannon, have sustained permanent damage. Not Mary Ingalls from the Little House on The Prairie, however: although scarlet fever is blamed for Mary's blindness, recent historical-scientific research lays the blame on a tick-borne viral meningitis that was going the rounds on the prairie at that time. If you read enough 19thC literature, you'll come across several cases where the heroine is delicate. "It's her heart, poor thing", someone will say, "she took the scarlet fever and hasn't been the same since".  This is connected. A well-known complication of scarlet fever is called rheumatic fever when the hopped-up immune system, having killed all the Streptococcus is still spoiling for a fight . . . and turns to attack the valves of the heart. In some people, at some time, with some strains of GAS, there is sufficient molecular similarity between the cells of the heart valves and the surface of Streptococcus that the immune system goes in flailing. It's similar to a dose of the runs from dodgy chicken  [ITCS, it's the Campylobacter, silly] developing into a frightening peripheral nerve degeneration called Guillain-BarrĂ© syndrome. Something similar is likely to be responsible for MS.

Now two other consequences of Strep infection have coursed over my horizon. PANDAS Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection which is a special case of PANS Pediatric Acute-onset Neuropsychiatric Syndrome.  I'm primed for stuff about OCD because one of my students did a research project on the genetic basis of the condition this last year. Turns out that following a case of Strep-throat, some children start washing their hands a lot or develop motor or verbal tics, seemingly over-night. They have enlarged basal ganglia in their brains when compared to age-matched peers without PANDAS. The current hypothesis being that, through molecular mimicry, the immune system is making antibodies that destroy key motor and cognitive control neurons in the brain.

4 comments:

  1. And post streptococcal glomerulonehritis! https://medlineplus.gov/ency/article/000503.htm
    What on earth is the connection?

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    1. The connexion must be the same as rheumatic fever. Some similarity in the structure of a protein in the membrane of cells of the heart valves and the cells of the kidney nephrons is considered by the immune system to resemble a protein on the surface of the Streptococcus. The strep-primed immune system will destroy such cells as effectively as it will nobble cancer cells if the triggers are in place. Dr Pedant points out that it is glomerulonePhritis only because it reminds me of a joke. Little Jimmy asks teacher for a toilet break; she requires him to recite the alphabet first; he desperately gallops off with ABCDEFGEHIJKLMNOQRSTUVWXYZ; teacher asks 'Where's the P' . . . 'running down my leg'. Bruhahahaha

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    2. I can't explain the spelling not the spacing! I wondered why the same antigen like proteins are found on those different structures. Heart is endothelium but isn't the nephron epithelium?

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  2. I don't know it's a mystery. https://www.youtube.com/watch?v=jTQurAEmt64. But the proteins involved don't have to be identical. The immune system recognises not the whole protein but an epitope of 8-12 amino acids. This might be the same or sufficiently similar in two different membrane bound proteins. otoh, your response to Strep doesn't have to match mine. Your immune system could clag onto one target protein similar to kidney and mine to another. But Maybe it IS the same protein. We only have 23,000 protein coding genes they all have to multi-task to a certain extent and it is not inconceivable that the same protein has a role in those two different tissues. Do 'they' even know which protein is affected in either disease? Is there a trained researcher in the house?

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