Strep/PANDAS symptoms

[kim]

I am 90% certain that my boys inherited a genetic mutation that resulted in a decreased cellular expression of Heparan sulfate.

 

I was trying to find out how this might be related to interactions with strep. It appears to me that the amt. of heparan sulfate on the host cells (the host being my son's) had some effect on what type of strep they may or may not be most be most susceptable to, as heperan sulfate will mediate the interaction btwn the ability of strep to invade a cell or remain extracellular. Some of this info is older, and I'm keeping in mind the the article that I posted that seemed to say that some strep has developed the ability to survive in the phagocytes. These are a type of white blood cell that are meant to eat bacterial cells and other garbage from what I gather (tricky hau?).

 

Heparan sulfate is a sugar chain attached to a core protein and is known as a (Gag) or glu- co- sa- min- o -gly- can. I asked about this on another thread, but I don't think anyone really knows what I'm talking about, so I'm trying to simplify here.

 

Group A strep expresses a virulence factor known as an M protein. Some strep is encapsulated with hyaluronan which is a substance that is also found in the human body/brain (again tricky bacteria). The first study appears to says that the amt. and type of GAG expressed on the cell surface will make you more or less susceptable to different strains of strep (heperan sulfate will mediate btwn the host cell and certain strains of strep).

 

What I would really like to know is if any autoimmune response to the capsular component hyaluronan of GAS (group a strep) has ever been studied as causing PANDAS symptoms. Does anyone have time to look for this info? It seems as if strain of strep that have this type of capsule would be a prime suspect.

 

If my guys express less heparan sufate because of their genes, it looks to me like this would apply to them, which would explain why they didn't show PANDAS symptoms, but DID have repeated strep infections that required 3 rounds of antibiotics in some instances, but no symptoms of an autoimmune/brain response (except clearly noted during my youngest sons last strep infection, which seems to have coincided with an intestinal viral infection (so which one was the culprit?)

 

I would also like to know if any of the clearly PANDAS kids here, exhibit PANDAS flares with some culture confirmed strep infections but not others.

 

Anyway I guess I'll post as breif of excerps here as possible and see if anyone has any opinions. I probably got too technical again, but I just don't know anyway around it.

 

http://www.ispub.com/ostia/index.php?xmlPr...1/rheumatic.xml

 

 

Pathogenesis of GAS infection

In the log phase of growth, streptococci divide approximately every 20 minutes. Only when they do so are they rapidly killed by penicillin. When phagocyted, they are also readily killed because they are highly susceptible to the antibacterial action of oxygen radicals and other antibacterial substances within phagosomes of white blood cells. Thus, streptococcal infection is principally extracellular, and its virulence relates primarily to resistance to phagocytosis and subsequent invasiveness and toxin production. Strains deficient in both the surface M protein and hyaluronate capsule are killed by phagocytes. Because capsular hyaluronate is virtually non-antigenic whereas M protein is exquisitely type-specific, immunologic protection against virulent strains is primarily dependent upon the action of homologous type anti-M antibodies ( 5 ). The multiplicity of M types therefore accounts for the repetitive nature of GAS infections and thus for recurrent bouts of RF .Resistance to phagocytosis is further enhanced by several anti-complementary effects of M protein, and by its precipitation of fibrinogen on the bacterial surface. In addition, the hyaluronate capsule itself disrupts connections of epithelial cells and promotes invasion of deeper tissues ( 6 ). The hyaluronate capsule also resists internalization of the organism by epithelial cells ( 7 ) or by skin keratinocytes ( 8 , 9 ). Benign, persistent throat carriage may result from epithelial cell internalization of less encapsulated strains where they may grow more slowly and be less readily eradicated by penicillin

 

 

 

 

http://www.blackwell-synergy.com/doi/full/...33.2003.03600.x

 

Several microbial pathogens have been reported to interact with glycosaminoglycans (GAGs) on cell surfaces and in the extracellular matrix. Here we demonstrate that M protein, a major surface-expressed virulence factor of the human bacterial pathogen, Streptococcus pyogenes, mediates binding to various forms of GAGs. Hence, S. pyogenes strains expressing a large number of different types of M proteins bound to dermatan sulfate (DS), highly sulfated fractions of heparan sulfate (HS) and heparin, whereas strains deficient in M protein surface expression failed to interact with these GAGs. Soluble M protein bound DS directly and could also inhibit the interaction between DS and S. pyogenes. Experiments with M protein fragments and with streptococci expressing deletion constructs of M protein, showed that determinants located in the NH2-terminal part as well as in the C-repeat region of the streptococcal proteins are required for full binding to GAGs. Treatment with ABC-chondroitinase and HS lyase that specifically remove DS and HS chains from cell surfaces, resulted in significantly reduced adhesion of S. pyogenes bacteria to human epithelial cells and skin fibroblasts.

and

Together with the finding that exogenous DS and HS could inhibit streptococcal adhesion, these data suggest that GAGs function as receptors in M protein-mediated adhesion of S. pyogenes.

 

 

This is a study that connects the hyaluronan part of what i'm talking about. Remember the ECM ia just referring to the extra cellular matrix wich is a web like area found just out side of a cell.

 

 

http://www.researchcrossroads.com/index.ph...rant_id=2234120

 

The extracellular matrix (ECM) of the brain is rich in hyaluronan and hyaluronan-binding molecules, suggesting that hyaluronan is the pivotal element of the brain ECM. However, being a pure polysaccharide, functional studies on hyaluronan suffered from the lack of molecular tools to directly manipulate its expression. Cloning of mammalian hyaluronan synthases has enabled to conduct studies aimed at directly addressing this issue. In this proposal, we will employ the Cre/lox-based conditional knockout technology to disrupt the hyaluronan synthase Has2 in each of the three major neural cell types, thereby generating mice in which hyaluronan synthesis is abolished specifically in respective cell types. In the first aim, we will disrupt hyaluronan synthesis in neural stem cells.

 

 

I am trying to find the results of this study, but time is being eaten alive with all of this!