ORCID Profile
0000-0003-2045-6788
Current Organisation
University of Oxford
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-04-2010
Abstract: HIV-positive in iduals who are infected with nontyphoidal strains of Salmonella enterica often succumb to high morbidity and mortality. Why this is the case is unknown. MacLennan et al. (p. 508 see the Perspective by Moir and Fauci ) have uncovered a dysregulated antibody response to Salmonella that is the likely culprit. Sera from HIV-infected in iduals do a poor job of killing S. Typhimurium, despite surprisingly elevated antibody titers. Experiments showed that HIV-infected serum inhibited the power of normal serum to kill Salmonella . Inhibition was specific to antibodies against lipopolysaccharide (LPS), a component of the cell wall of Salmonella . Hence, HIV-infected sera was able to kill Salmonella strains lacking LPS, and removing LPS immunoglobulin G from infected sera permitted Salmonella killing. Thus, not only does HIV cause defects in cell-mediated immunity but it also seems to impair humoral immunity, with severe consequences for multiple infections.
Publisher: Springer Science and Business Media LLC
Date: 12-2022
DOI: 10.1038/S41591-022-02095-5
Abstract: Treatment with immune checkpoint blockade (ICB) frequently triggers immune-related adverse events (irAEs), causing considerable morbidity. In 214 patients receiving ICB for melanoma, we observed increased severe irAE risk in minor allele carriers of rs16906115, intronic to IL7 . We found that rs16906115 forms a B cell-specific expression quantitative trait locus (eQTL) to IL7 in patients. Patients carrying the risk allele demonstrate increased pre-treatment B cell IL7 expression, which independently associates with irAE risk, ergent immunoglobulin expression and more B cell receptor mutations. Consistent with the role of IL-7 in T cell development, risk allele carriers have distinct ICB-induced CD8 + T cell subset responses, skewing of T cell clonality and greater proportional repertoire occupancy by large clones. Finally, analysis of TCGA data suggests that risk allele carriers independently have improved melanoma survival. These observations highlight key roles for B cells and IL-7 in both ICB response and toxicity and clinical outcomes in melanoma.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-09-2019
Abstract: The FPN Q248H mutation protects children from anemia, hemolysis, and iron deficiency, but not malaria or bacterial infection.
Publisher: Springer Science and Business Media LLC
Date: 14-07-2022
DOI: 10.1038/S41467-022-31626-4
Abstract: Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans ( n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY , MC1R and UVSSA . Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for James J Gilchrist.