Use of gene expression profiling to identify candidate genes for pretherapeutic patient classification in acute appendicitis

• Published in: BJS open Vol. 5; no. 1
• Main Authors: Kiss, N, Minderjahn, M, Reismann, J, Svensson, J, Wester, T, Hauptmann, K, Schad, M, Kallarackal, J, von Bernuth, H, Reismann, M
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.01.2021
• Subjects: Acute Disease; Adolescent; Appendicitis - classification; Appendicitis - genetics; Child; Female; Gangrene; Gene Expression Profiling; Humans; Leukocytes, Mononuclear - pathology; Male; Medicin och hälsovetenskap; Microarray Analysis; Original; Prospective Studies
• ISSN: 2474-9842; 2474-9842
• DOI: 10.1093/bjsopen/zraa045

Phlegmonous and gangrenous appendicitis represent independent pathophysiological entities with different clinical courses ranging from spontaneous resolution to septic disease. However, reliable predictive methods for these clinical phenotypes have not yet been established. In an attempt to provide pathophysiological insights into the matter, a genomewide gene expression analysis was undertaken in patients with acute appendicitis. Peripheral blood mononuclear cells were isolated and, after histological confirmation of PA or GA, analysed for genomewide gene expression profiling using RNA microarray technology and subsequent pathway analysis. Samples from 29 patients aged 7-17 years were included. Genomewide gene expression analysis was performed on 13 samples of phlegmonous and 16 of gangrenous appendicitis. From a total of 56 666 genes, 3594 were significantly differently expressed. Distinct interaction between T and B cells in the phlegmonous appendicitis group was suggested by overexpression of T cell receptor α and β subunits, CD2, CD3, MHC II, CD40L, and the B cell markers CD72 and CD79, indicating an antiviral mechanism. In the gangrenous appendicitis group, expression of genes delineating antibacterial mechanisms was found. These results provide evidence for different and independent gene expression in phlegmonous and gangrenous appendicitis in general, but also suggest distinct immunological patterns for the respective entities. In particular, the findings are compatible with previous evidence of spontaneous resolution in phlegmonous and progressive disease in gangrenous appendicitis.