Browsing by Author "Mcdonald, Braedon"

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    Monocyte Phenotyping as a Biomarker to Improve the Diagnosis of Acute Pediatric Appendicitis
    (2022-12-15) Lau, Matthew; Thompson, Graham; Jenne, Craig; Mcdonald, Braedon; Twilt, Marinka
    Acute appendicitis is currently the most common reason for surgery in children. If left untreated, appendicitis can progress to appendiceal perforation, sepsis, and death. Despite being a common disease in children, the diagnosis of AA in pediatric populations remains challenging. Children entering the emergency department often present with non-specific abdominal pain and due to differences in developmental milestones, variable clinical presentations based on age, and difficulty in visualization of the organ with common diagnostic approaches such as ultrasound, appendicitis may be over-diagnosed or misdiagnosed entirely. To date, no single biomarker has been shown to have both sufficient sensitivity and specificity to conclude appendicitis. More recent research has discovered that children with AA display a unique cytokine pattern when compared to children with non-appendicitis abdominal pain. One significant component of this cytokine pattern was an increase in monocyte chemoattractant protein 1 in children with appendicitis. MCP-1 is a powerful attractant of monocytes, particularly members of the classical monocyte subset. We hypothesized that an increase in MCP-1 would create a shift in peripheral monocyte subset populations, with a decrease in classical phenotypes favoring an increase in intermediate and non-classical monocytes. No study has yet attempted to understand the effects of acute pediatric appendicitis on immune cell subsets, specifically, peripheral blood monocytes. We developed a mass cytometry protocol to explore monocyte and other immune cell subsets in peripheral blood samples taken from children attending the emergency department with suspected appendicitis. Through differential marker analysis we concluded that there were no significant differences in the proportions of any monocyte subsets between AA and NAAP patients. However, differential abundance analysis of the total immune cell panel determined that T cell, B cell, and natural killer cell populations were higher in NAAP than AA. Further marker expression analysis uncovered an increase in CD184 neutrophils in children with NAAP versus those with AA.