A Little Poisoning Along the Road to ME/CFS
Looking at my symptoms, many of which are far less these days and some are gone, it would be easy to figure that I'd just been dealing with some heavy-duty menopausal issues.
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Autoantibodies activiating beta 2 and musc receptor vasodilation in idiopathic OI

Discussion in 'Latest ME/CFS Research' started by ramakentesh, Feb 20, 2012.

  1. ramakentesh

    ramakentesh Senior Member

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    http://www.ncbi.nlm.nih.gov/pubmed/22215709

    Agonistic autoantibodies as vasodilators in orthostatic hypotension: a new mechanism.

    Li H, Kem DC, Reim S, Khan M, Vanderlinde-Wood M, Zillner C, Collier D, Liles C, Hill MA, Cunningham MW, Aston CE, Yu X.


    Source

    Endocrinology and the Heart Rhythm Institute, University of Oklahoma Health Sciences Center, TCH 6E103, 1200 Everett Dr, Oklahoma City, OK 73104.


    Abstract

    Agonistic autoantibodies to the ?-adrenergic and muscarinic receptors are a novel investigative and therapeutic target for certain orthostatic disorders. We have identified the presence of autoantibodies to ?2-adrenergic and/or M3 muscarinic receptors by ELISA in 75% (15 of 20) of patients with significant orthostatic hypotension. Purified serum IgG from all 20 of the patients and 10 healthy control subjects were examined in a receptor-transfected cell-based cAMP assay for ?2 receptor activation and ?-arrestin assay for M3 receptor activation. There was a significant increase in IgG-induced activation of ?2 and M3 receptors in the patient group compared with controls. A dose response was observed for both IgG activation of ?2 and M3 receptors and inhibition of their activation with the nonselective ? blocker propranolol and muscarinic blocker atropine. The antibody effects on ?2 and/or M3 (via production of NO) receptor-mediated vasodilation were studied in a rat cremaster resistance arteriole assay. Infusion of IgG from patients with documented ?2 and/or M3 receptor agonistic activity produced a dose-dependent vasodilation. Sequential addition of the ?-blocker propranolol and the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester partially inhibited IgG-induced vasodilation (percentage of maximal dilatory response: from 57.710.4 to 35.34.6 and 24.35.8, respectively; P<0.01; n=3), indicating that antibody activation of vascular ?2 and/or M3 receptors may contribute to systemic vasodilation. These data support the concept that circulating agonistic autoantibodies serve as vasodilators and may cause or exacerbate orthostatic hypotension.
     
  2. OverTheHills

    OverTheHills

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    New Zealand
    Thanks for posting this Ramakentesh, can anyone explain/discuss this a little more?

    To my overactive and completely untrained mind I'm hearing OI (a very common comorbidity in ME) may have an autoimmune cause which is intersting given the autoimmune theory of ME advanced by the norwegians. Or is that just my brain floss talking? OTH.
     
  3. natasa778

    natasa778 Senior Member

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    London UK
    Very interesting, thanks for posting. Here is one on muscarinic autoantibodies and dysautonomia in SS

    http://www.ncbi.nlm.nih.gov/pubmed/10902771

    Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjgren's syndrome

    Sjgren's syndrome (SS) is an autoimmune disorder characterized by dry eyes and mouth (sicca syndrome) and lymphocytic infiltration of the lacrimal and salivary glands. Abnormalities of parasympathetic neurotransmission may contribute to the glandular dysfunction. In this study, we used a functional assay to investigate autoantibody-mediated effects on parasympathetic neurotransmission and smooth muscle contraction.

    ...
    Autoantibodies that act as antagonists at M3-muscarinic receptors on smooth muscle occur in a subset of patients with primary and secondary SS. Their presence in secondary SS was unexpected and provides new evidence for a common pathogenetic link between primary and secondary SS. These autoantibodies appear to contribute to sicca symptoms and may explain associated features of autonomic dysfunction in some patients.
     
  4. Valentijn

    Valentijn Activity Level: 3

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    I think you're correct, though they're just proposing that autoimmune problems are just one possible cause of OI, or the cause of a specific type of OI. There are plenty of other causes of OI too, and plenty of different types of OI.
     
  5. natasa778

    natasa778 Senior Member

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    autoimmune mechanisms in pathogenesis of dementia

    this is also interesting:

    ... Our data support the notion that autoimmune mechanisms play a significant role in the pathogenesis of Alzheimer's and vascular dementia. We suggest that agonistic autoantibodies to the ?(1) -adrenergic and the ?(2) -adrenergic receptor may contribute to vascular lesions and increased plaque formation.

    http://www.ncbi.nlm.nih.gov/pubmed/22260197
     
  6. natasa778

    natasa778 Senior Member

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    Autoimmunity against the ?(2) adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome


    http://www.ncbi.nlm.nih.gov/pubmed/21816540

    Herein, we demonstrate the presence of autoantibodies in a subset of CRPS patients with agonistic-like properties on the ?(2) adrenergic receptor and/or the muscarinic-2 receptor.
     
  7. natasa778

    natasa778 Senior Member

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    London UK
  8. ramakentesh

    ramakentesh Senior Member

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    thanks for adding all those wonderful links guys. Some really interesting stuff in there. I wish these autoantibodies had been checked in OI earlier. Id also be interested in results from POTS patients.
     

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