{
  "abstract": "Introduction Environmental Enteropathy (EE) is a subclinical disorder of the small intestine in people living in tropical or insanitary environments, leading to disrupted barrier function. This disruption drives microbial translocation, chronic systemic inflammation and impaired nutrient absorption. Most research on EE in impoverished populations has relied on immune function surrogates with no interrogation of immune cell phenotypes characterising this gut–blood crosstalk. We aimed to test the hypothesis that monocyte activation, T cell activation and exhaustion are worse in adults from low socio-economic status (SES) compared to those from high-SES groups, within the same population.Methods We enrolled 76 adults from low-SES and 26 from high-SES communities and performed a cross-sectional comparison at a single time point. Enzyme-linked immunosorbent assay measured C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), intestinal fatty acid-binding protein (iFABP), Endotoxin-core antibodies (IgG, IgA, IgM), soluble CD163, soluble CD14, and lipopolysaccharide-binding protein (LBP), while stool samples were used to measure Myeloperoxidase (MPO). Monocyte expression of CD86, TLR4, and HLADR, together with T cell expression of CD127, FOXP3, PD-1, and α4β7 were analysed in buffy coats. Statistical comparisons used Mann-Whitney or t-tests as appropriate, followed by principal component analysis (PCA), and linear regression, which assessed PC associations with duodenal morphometry.Results Adults of low SES had significantly higher plasma concentrations of iFABP ( P=0.003), Endotoxin-core IgG (P< 0.0001), IgA (P=0.002), and IgM (P= 0.001), LBP (P< 0.0001), sCD163 (P= 0.027), and sCD14 (P< 0.0001), but not MPO, CRP or AGP. Additionally, low SES adults had higher Median Fluorescence intensities (MFIs) for CD86 (P< 0.0001) and TLR-4 (P< 0.0001), but not HLADR (P= 0.131), on total monocytes and across all subclasses. These low SES adults also had higher proportions of CD4+CD127lowFOXP3+ (P< 0.0001), CD4+α4β7+CD127lowFOXP3+ (P< 0.0001), CD4+α4β7+ (P< 0.0001), CD4+PD-1+ (P< 0.0001), CD4+α4β7+PD-1+ (P< 0.0001), CD8+α4β7+ (P< 0.0001), CD8+PD-1+ (P< 0.0001), CD8+α4β7+PD-1+ (P< 0.0001) and higher CD4+CD127lowFOXP3+ expression of PD-1 (P< 0.0001). PC1, comprised of monocyte activation and CD4+CD127lowFOXP3+ T cell expression of PD-1, was positively associated with villus width (Adj coeff= 4.1; P= 0.012), and negatively with villus height (Adj coeff= -4.7; P= 0.009).Conclusion We present evidence of epithelial injury and microbial translocation, which increases monocyte activation. Additionally, we provide evidence of a recirculating, dampened T cell phenotype, marked by increased Tregs and PD-1-expressing T cells, providing a mechanistic link between EE and systemic immune dysfunction.",
  "authors": [
    {
      "affiliations": [
        "Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia",
        "University of Glasgow, Glasgow, Scotland"
      ],
      "name": "Tracy Naomi Phiri"
    },
    {
      "affiliations": [
        "Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia"
      ],
      "name": "Enala Musheba"
    },
    {
      "affiliations": [
        "Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia",
        "Queen Mary of London, London, England"
      ],
      "name": "Paul Kelly"
    },
    {
      "affiliations": [
        "Tropical Gastroenterology and Nutrition Group, Lusaka, Zambia",
        "University of Glasgow, Glasgow, Scotland"
      ],
      "name": "Claire D Bourke"
    }
  ],
  "title": "O16 Adults from a low socio-economic status living with environmental enteropathy have a dampened systemic T cell immune phenotype",
  "uid": "8812d1ec-1955-5fbe-b2c1-abb2191ca9d9"
}