Associations of Immune Genetic Variability with Gulf War Illness

Violeta

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What can we learn about ME/CFS from Gulf War Illness research?

Associations of Immune Genetic Variability with Gulf War Illness in 1990–1991 Gulf War Veterans from the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615505/

In particular, myelin and neuronal breakdown products in the extracellular spaces are thought to activate glial cells by acting as toll-like receptor (TLR) agonists, specifically at TLR4 [11,12]. Glial activation of TLR4 from these internal factors (including HMGB1 [13]), as well as external stimuli (e.g., cellular debris, bacteria) results in release of CNS pro-inflammatory cytokines (e.g., interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)). The CNS inflammatory response [14] induces sickness response symptoms including fatigue, muscle and joint pain and cognitive difficulties.

However, what is less clear is why only some GW veterans have chronic illness while others with similar exposures do not, and may be suggestive of variability in genetic susceptibility for chronic inflammation or risk susceptibility of GWI.
 

Violeta

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TLR4

Toll-like receptor 4 (TLR4) is a transmembrane protein that plays a key role in the body's innate immune response, particularly in fighting bacterial infections:


  • Function
    TLR4 is a pattern recognition receptor that detects pathogen-associated molecular patterns (PAMPs). It's best known for recognizing lipopolysaccharide (LPS), a component of many gram-negative bacteria, but it can also bind to viral proteins, polysaccharides, and other molecules.


  • Activation
    When TLR4 is activated, it produces cytokines that are pro-inflammatory, antiviral, and anti-bacterial. TLR4 is unique among TLRs because it can activate both MyD88-dependent and TRIF-dependent signaling pathways.


    • Role in disease
      TLR4 plays a role in many diseases, including:

        • Chronic liver disease: TLR4 signaling is a key factor in the development of chronic liver diseases like alcoholic liver disease, nonalcoholic fatty liver disease, and chronic hepatitis C.

        • Alzheimer's disease: TLR4 expression is associated with increased uptake of amyloid beta peptide (Aβ), which is closely linked to brain inflammation.

        • Urinary tract infections: TLR4 promoter sequence variation has been linked to human UTI susceptibility.

 
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