Markers of neutrophil activation and extracellular trap formation predict appendicitis

BACKGROUND: Although appendicitis is one of the most frequently occurring pediatric surgery emergencies, current biomarkers for diagnosis are unspecific and have low predictive values. Neutrophils are an essential component of the innate immune system involved during appendicitis. Thus, the current study aimed to evaluate neutrophils and their activation markers in a prospective cohort study.

METHODS: The study population included all children with acute abdominal pain who presented to the pediatric surgery department of 2 large clinics between July 2018 and December 2019. All enrolled subjects underwent blood sample collection with an assessment of white blood cell count, C-reactive protein, cell-free DNA, neutrophil elastase, myeloperoxidase, and citrullinated histone H3. If an appendectomy was performed, the appendix was stained for myeloperoxidase, neutrophil elastase, and citrullinated histone H3 using immunofluorescence.

RESULTS: In total, 198 subjects were included in the study, of whom 133 had histological verified appendicitis. In those with appendicitis, white blood cell count and C-reactive protein showed a moderate diagnostic value for (noncomplicated and complicated) appendicitis. However, cell-free DNA (area under the curve .87) and citrullinated histone H3 (area under the curve .88) demonstrated excellent predictive power for appendicitis. Most notably, citrullinated histone H3 was able to distinguish (1) noncomplicated from complicated appendicitis, and (2) predict patient outcome. Moreover, the examined biomarkers appear to reflect tissue expression and disease severity.

CONCLUSION: Markers of neutrophil activation and extracellular trap formation are excellent biomarkers for appendicitis. In particular, citrullinated histone H3 may be used to identify children with an increased risk of developing complications after appendicitis.