Gene expression patterns associated with influenza A and type I hypersensitivity in childhood appendicitis

Both influenza A infection (IAV) and type I hypersensitivity mechanisms have been independently linked to acute appendicitis. Particularly the expression of type I hypersensitivity associated with cytokine interleukin (IL) 13 has been shown to be of significance in both, appendicitis and influenza infection. The aim of the current study was to analyze possible associations of respective gene expressions at the level of mathematical correlations.

We analyzed messenger RNA (mRNA) gene expressions of IAV-associated markers, hypersensitivity type I-related cytokines and inflammatory markers IL-17A and c-reactive protein (CRP) in peripheral blood mononuclear cells from 29 children aged 7-17 years, who were operated for histologically confirmed appendicitis at Charité-Universitätsmedizin Berlin between April and August 2019. Statistical relationships between gene expressions were investigated using Spearman's correlation analysis, with a correlation coefficient r ≥ 0.5 or r ≤ - 0.5 representing high, and r ≥ 0.7 or r ≤ - 0.7 very high correlations. Statistical significance was assumed at P < 0.01.

A total of 29 patients were involved in this study. Particularly the expression of IL-13 showed highly significant negative correlations with that of IAV-specific antiviral response genes, ranging from - 0.89 (P < 0.0001) to - 0.49 (P = 0.006). A strong inflammatory background was demonstrated by very high correlations of IL-13 with CRP (r = 0.91, P < 0.0001) and IL-17A (r = 0.82, P < 0.0001).

These findings suggest a connection between IAV infection and acute appendicitis in children, implicating sequential immune responses, including hypersensitivity type I mechanisms, in appendicitis pathophysiology.