Lymphocyte and not monocyte-associated genes are upregulated in moderately severe acute pancreatitis

Abstract

Purpose: The role of lymphocyte and monocyte-associated genes in the pathophysiology of acute pancreatitis (AP) have not been widely studied. This study aimed at determining the expression levels of these cell-associated genes early in AP severity to assist with stratification. Methods: Whole blood was sampled from twenty-nine patients (Ethics #M180133) consisting of 14 moderate (MSAP), 10 moderately severe (MSAP) and 5 severe (SAP), three days post-onset of epigastric pain. Total RNA was extracted from peripheral blood mononuclear cells of 13 (MAP=7, MSAP=4, SAP=2) patient samples and cDNA synthesised for use in profiling genes in a pre-screen. An RT2 Profiler PCR kit was used to profile the expression of ninety-six innate and adaptive immune genes. NOD1 was further analysed in all samples based on its expression level to validate findings. Using flow cytometry, the frequency of lymphocyte and monocytes was determined. Results: An association was reported between severity/white blood cell count (rs=0.649) and severity/length of hospital stay (rs=0.974). Lymphocyte-associated genes such as IL10 was upregulated in MSAP group while monocytes-associated genes such as NOD1 was downregulated compared to the SAP group, with NOD1 being the most downregulated in MSAP (Table 1). Validation results at day three showed a six-fold decrease in NOD1 in the MSAP group compared to MAP with levels normalising with time. Congruent to gene levels, the frequency of lymphocytes/monocytes ratio in MSAP patients was higher. Conclusion: The upregulation of lymphocyte-associated genes, the corresponding higher lymphocyte to monocyte frequency can distinguish MSAP from MAP and potentially from SAP patients. Validation studies are ongoing for other genes.Table 1: Fold regulation results from RT2 Profiler array (bold; commonly expressed by lymphocytes, not bold; commonly expressed by monocytes )Gene SymbolMild (MAP)Moderate (MSAP)Severe (SAP)IL10-1.3058.62-1.47IL13-1.9283.6619.53IL17A1.72116.932.56IL23A-5.6018.076.57IL4-1.13108.6436.83IL51.33192.591.21NOD1-8.93-14.6264.21TLR1-1.098.4012.95GAPDH1.383.4744.64 Open table in a new tab