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Decoding the Genetic Basis of Mast Cell Hypersensitivity and Infection Risk in Hypermobile Ehlers-Danlos Syndrome, 2024, Purusha Shirvani

Discussion in 'Other health news and research' started by Mij, Nov 1, 2024.

  1. Mij

    Mij Senior Member (Voting Rights)

    Messages:
    9,750
    Abstract
    Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder marked by joint hypermobility, skin hyperextensibility, and tissue fragility. Recent studies have linked hEDS with mast cell activation syndrome (MCAS), suggesting a genetic interplay affecting immune regulation and infection susceptibility.

    This study aims to decode the genetic basis of mast cell hypersensitivity and increased infection risk in hEDS by identifying specific genetic variants associated with these conditions.

    We conducted whole-genome sequencing (WGS) on 18 hEDS participants and 7 first-degree relatives as controls, focusing on identifying genetic variants associated with mast cell dysregulation. Participants underwent clinical assessments to document hEDS symptoms and mast cell hypersensitivity, with particular attention to past infections and antihistamine response.

    Our analysis identified specific genetic variants in MT-CYB, HTT, MUC3A, HLA-B and HLA-DRB1, which are implicated in hEDS and MCAS. Protein–protein interaction (PPI) network analysis revealed significant interactions among identified variants, highlighting their involvement in pathways related to antigen processing, mucosal protection, and collagen synthesis. Notably, 61.1% of the hEDS cohort reported recurrent infections compared to 28.5% in controls, and 72.2% had documented mast cell hypersensitivity versus 14.2% in controls.

    These findings provide a plausible explanation for the complex interplay between connective tissue abnormalities and immune dysregulation in hEDS. The identified genetic variants offer insights into potential therapeutic targets for modulating mast cell activity and improving patient outcomes.

    Future research should validate these findings in larger cohorts and explore the functional implications of these variants to develop effective treatment strategies for hEDS and related mast cell disorders.
    LINK
     
    Mij, Nov 1, 2024
    #1
    Deanne NZ, Trish and Peter Trewhitt like this.
  2. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Location:
    London, UK
    Chris Ponting might feel a bit miffed that these people got an answer with 18 patients instead of 18,000.
     
    Jonathan Edwards, Nov 1, 2024
    #2
    Deanne NZ, EndME, Peter Trewhitt and 1 other person like this.
  3. Trish

    Trish Moderator Staff Member

    Messages:
    55,962
    Location:
    UK
    I glanced through to try to find out how participants were selected. It seems they contacted some of their existing hEDS patients to invite them and the patients selected their relatives to be controls?? Surely that brings in huge biases. The hEDS patients would only have been attending the clinic if they had health problems, so were already skewed towards those who might have allergies etc, and their relatives, if chosen by the patient, may have been consiously or unconsciously selected because by contrast they were healthy and didn't have allergy problems.

    I wonder what would happen if they did it the other way around, asked a group of allergy patients without bendy joints to be one group, and ask them to select a healthy relative with bendy joints to be their 'control'.
     
    Trish, Nov 1, 2024
    #3
    alktipping, Deanne NZ and Peter Trewhitt like this.

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