Link between POTS, MCAS and CFS - Innate inflammation in response to an antigen..t-cell exhaustion's role?

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31:00 onwards Dr Grubb explains which autoantibodies are found in POTS and suggests they are driven firstly by the innate immune system, including mast cell mediators and other cytokines, which then triggers the adaptive immune system to make autoantibodies . He argues it can't be coincidence that 82% of the POTS patients have platelet storage pool deficiency. Platelets are the first line of defence and trigger the rest of the immune system to work, suggesting the innate immune system's primary role. Its like the innate immune system has gone haywire and is throwing out all these inflmmatory cytokines. It reminded me of what Dr Lisa Selin says about mast cells causing endless inflammation as a result of t-cell exhaustion after a virus or Lyme etc. She suggests T-cell exhaustion and the subsequent inlfammatory response causes CFS picture

So both Drs suggest innate immune inflammation is causing most of the problems, although Dr Grubb does not mention T-Cell exhaustion or CFS as he is focussing solely on POTS. Could it be that T-cell exhaustion leads to chronic autoinflammation (including MCAS) in response to the antigen that cannot be cleared. Then the adaptive immune system responds to this by forming autoantibodies, such as A1 adrenergic and M4 Muscarinic, and you end up with POTS too. Could this be why so many of us have all three - CFS, MCAS and POTS?
 
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Violeta

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This may not be the root cause, but BH4 does have a part in T-Cell production.

"Genetic regulators and environmental stimuli modulate T cell activation in autoimmunity and cancer. The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine neurotransmitters, the generation of nitric oxide, and pain. Here we uncover a link between these processes, identifying a fundamental role for BH4 in T cell biology."

"Kynurenine—a tryptophan metabolite that blocks antitumour immunity—inhibits T cell proliferation in a manner that can be rescued by BH4."

The metabolite BH4 controls T cell proliferation in autoimmunity and cancer
Cronin, Seehus, and Penninge

https://www.nature.com/articles/s41586-018-0701-2
 
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This may not be the root cause, but BH4 does have a part in T-Cell production.

"Genetic regulators and environmental stimuli modulate T cell activation in autoimmunity and cancer. The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine neurotransmitters, the generation of nitric oxide, and pain. Here we uncover a link between these processes, identifying a fundamental role for BH4 in T cell biology."

"Kynurenine—a tryptophan metabolite that blocks antitumour immunity—inhibits T cell proliferation in a manner that can be rescued by BH4."

The metabolite BH4 controls T cell proliferation in autoimmunity and cancer
Cronin, Seehus, and Penninge

https://www.nature.com/articles/s41586-018-0701-2
Interesting. If the Metabolic Trap theory is correct we would have less kynurenine and so is the suggestion that T cells would continue to proliferate? Could this lead to t cell exhaustion?