Peripheral Lymphocytes of Patients with Inflammatory Bowel Disease Have Altered Concentrations of Key Apoptosis Players: Preliminary Results

Abstract

Notwithstanding uncertain pathogenesis of inflammatory bowel disease (IBD), deregulation of adaptive immunity is paramount for the development of inflammation. Essential role in the resolution of inflammation is played by apoptosis, deregulated in lymphocytes isolated from inflamed intestine. Despite IBD being a systemic disease, little is known about apoptosis of peripheral lymphocytes. The concentrations of Bcl-2, cytochrome c, p53, and caspase-9 were determined (ELISA) in lymphocyte-enriched fractions of peripheral blood mononuclear cells (LE-PBMCs) from 64 individuals (42 with IBD) and related to IBD phenotype and activity, treatment, and inflammatory and hematological indices. The diagnostic potential of evaluated markers was determined as well. All evaluated molecules were significantly lower in IBD patients, of which cytochrome c and p53 were significantly lower exclusively in patients with Crohn's disease (CD) and cytochrome c differed significantly between CD and ulcerative colitis (UC). Caspase 9 was significantly lower in active IBD and Bcl-2 in active UC whereas cytochrome c was higher in active CD. Treatment with corticosteroids affected the concentrations of cytochrome c and p53. Both positively correlated with hsCRP and the concentrations of all markers were interrelated. As IBD markers, Bcl-2 and caspase-9 displayed good accuracy and, as a panel of markers with cytochrome c, their accuracy was excellent (92%). As CD markers Bcl-2, cytochrome c, and p53 displayed fair accuracy but combined determination of Bcl-2 and cytochrome c improved the accuracy to 85%. Taken together, our results imply diminished intrinsic apoptotic capacity of LE-PBMCs in IBD but an upregulation of proapoptotic features parallel to increasing severity of inflammation. Observed abnormalities in intrinsic pathway of apoptosis are more pronounced in CD. Upon positive validation on a larger set of patients, combined quantification of Bcl-2 and cytochrome c might be considered as an adjunct in differential diagnosis of UC and CD of colon and rectum.

Variants of the CASP9 gene as candidate markers for primary response to anti-TNF therapy in Crohn's disease patients

“…3). Our observations are consistent with the results obtained by Neubauer et al They assessed CASP-9 concentration in peripheral blood lymphocytes of patients with IBD by immunoenzyme method and showed signi cantly lower concentrations of CASP-9 in patients with active IBD compared to the control group (Neubauer et al 2018). A follow up study of our experiment was to determine CASP-9 mRNA expression in cell cultures of peripheral blood lymphocytes that were treated with IFX.…”

Research progress on the relationship between Paneth cells-susceptibility genes, intestinal microecology and inflammatory bowel disease

“…PCs are an important component of the intestinal epithelial barrier, so it is not surprising that functional abnormalities of PCs play a role in CD development[ 83 ]. The first pathological analysis of small intestine samples from CD patients revealed the presence of intracellular vesicle abnormalities in PCs in these patients[ 84 ].…”

Decreased expression of MUC2 due to a decrease in the expression of lectins and apoptotic defects in colitis patients

“…Both of these pathways also activate caspase, a protease that targets cellular proteins, triggering cell disassembly [ 20 ]. A previous study has revealed a decrease in intrinsic apoptosis in colitis compared to controls [ 21 ]. The role of apoptosis in colitis is also still controversial.…”