Dataset Information

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease.

ABSTRACT: Early stratification of the severity of acute pancreatitis (AP) is clinically important. Regulatory B cells have been found to be associated with disease activity of autoimmune diseases. However, the role of Regulatory B cells in AP remains unknown. We investigate the dynamic longitudinal changes in circulating IL-10-producing B cells (B10) and memory CD19+CD24hiCD27hi cells in patients with AP to evaluate their prediction utility for AP severity. B10, CD19+CD24hiCD27hi cells, inflammatory markers and cytokines were detected in patients with AP immediately after admission to the hospital (day 1), then on the third and seventh days. We observed decreases in lymphocytes, CD19+, B10, CD19+CD24hiCD27hi cells and lower mean fluorescence intensity (MFI) of CD80 and CD86 on B10 or CD19+CD24hiCD27hi cells in patients with AP, especially in those with severe acute pancreatitis (SAP). CD19+CD24hiCD27hi cells from patients with AP suppressed the cytokine productions of CD4+ T cells and CD14+ monocytes, but had impaired ability to induce regulatory T cells response. B10 and CD19+CD24hiCD27hi cells significantly increased in patients with mild acute pancreatitis (MAP) from day 1 to day 7, whereas these indexes remained stable in patients with SAP. B10 or CD19+CD24hiCD27hi cells were negatively correlated with the severity index (APACHE II score), inflammatory markers (C-reactive protein, CD64 index), and cytokines (IL-6, IL-17, TNF-?). Furthermore, receiver operating characteristic (ROC) curve analysis revealed that B10 and CD19+CD24hiCD27hi cells could predict the development of SAP. Thus, the detection of B10 and CD19+CD24hiCD27hi cells may be a practical way to improve the early assessment of AP severity.

SUBMITTER: Qiu L

PROVIDER: S-EPMC6281415 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease.

Qiu Liannv L Zhou Yonglie Y Yu Qinghua Q Yu Junde J Li Qian Q Sun Renhua R

Oncotarget 20180103 90

Early stratification of the severity of acute pancreatitis (AP) is clinically important. Regulatory B cells have been found to be associated with disease activity of autoimmune diseases. However, the role of Regulatory B cells in AP remains unknown. We investigate the dynamic longitudinal changes in circulating IL-10-producing B cells (B10) and memory CD19+CD24hiCD27hi cells in patients with AP to evaluate their prediction utility for AP severity. B10, CD19+ ...[more]

PMID: 30546828

Similar Datasets

Project description:Background & Aims Variants in the tumor necrosis factor superfamily member 15 gene (TNFSF15, also called TL1A) have been associated with risk for inflammatory bowel diseases (IBD). TL1A affects expression of multiple cytokines to promote mucosal inflammation. Little is known about the TL1A-response pathways that regulate cytokine expression. We investigated T-cell gene expression patterns to determine the mechanisms by which TL1A regulates cytokine production, and whether these associate with outcomes of patients with Crohn’s disease (CD).Methods Peripheral T cells isolated from normal donors were cultured with TL1A. We performed gene expression profile analysis, by RNA sequencing, of subsets of interferon gamma (IFNG)-producing and non-producing cells, purified by flow cytometry. Unsupervised hierarchical clustering analysis was used to identify gene expression differences between these subsets. Ribonuclease T2 gene (RNASET2) expression and methylation were assessed by quantitative trait loci analyses. Clinical characteristics of patients (complications, resistance to therapy, recurrence time) were associated with single nucleotide polymorphisms in RNASET2. We performed motif screening to identify polymorphisms that disrupt transcription factor binding sites. Levels of RNASET2 were knocked down with small interfering RNA in CD4+ T cells and the effect on protein expression was determined by proteomic analysis and cytokine production. Cell aggregation was measured by flow cytometry. ResultsWe identified 764 genes with at least a 2-fold difference in TL1A-mediated expression between IFNG-secreting and non-secreting T cells (P<1 × 10−5). Many of these genes were located near IBD susceptibility variants. RNASET2 was the only IBD risk-associated gene with greater than 5-fold downregulation in the IFNG-secreting subset. RNASET2 disease risk variants were associated with decreased expression in peripheral and mucosal tissues and DNA hypermethylation in CD patients requiring surgical intervention. RNASET2 disease risk variants were associated in CD patients with more complicated disease or resistance to therapy, defined in part by failed response to treatment, increased length of intestinal resection, shorter time to repeat surgery, and high Rutgeerts score (>2) in post-operative endoscopy. The RNASET2 variant rs2149092 was predicted to disrupt a consensus binding site for the transcription factor ETS within an enhancer region. Expression of RNASET2 correlated with expression of ETS. RNASET2 knockdown in T cells increased expression of IFNG and ICAM1 and induced T cells aggregation. A blocking antibody against LFA1, disrupting the LFA1-ICAM1 interaction, reduced T-cell production of IFNG. Conclusions We identified decreased expression of RNASET2 as a component of TL1A-mediated increase in production of IFNG and as a potential biomarker for patients with severe CD. Further study of the role of RNASET2 in regulating mucosal inflammation may lead to development of novel therapeutic targets.

Project description:We recently reported that deletion-type copy number variations of the T cell receptor (TCR) γ, α, and δ genes greatly enhanced susceptibility to multiple sclerosis (MS). However, the effect of abnormal TCR γδ gene rearrangement on MS pathogenesis remains unknown. In the present study, we aimed to clarify γδ TCR repertoire alterations and their relationship to clinical and immunological parameters in MS patients by comprehensive flow cytometric immunophenotyping. Peripheral blood mononuclear cells obtained from 30 untreated MS patients in remission and 23 age- and sex-matched healthy controls (HCs) were stained for surface markers and intracellular cytokines after stimulation with phorbol 12-myristate 13-acetate and ionomycin, and analyzed by flow cytometry. MS patients showed significantly decreased percentages of Vδ2+ and Vδ2+Vγ9+ cells in γδ T cells (pcorr = 0.0297 and pcorr = 0.0288, respectively) and elevated Vδ1/Vδ2 ratios compared with HCs (p = 0.0033). The percentages of interferon (IFN)-γ+Vδ2+ and interleukin (IL)-17A+IFN-γ+Vδ2+ cells in γδ T cells, as well as IFN-γ+ cells in Vδ2+ γδ T cells, were significantly lower in MS patients than in HCs (pcorr < 0.0009, pcorr = 0.0135, and pcorr = 0.0054, respectively). The percentages of Vδ2+ and Vδ2+Vγ9+ cells in γδ T cells were negatively correlated with both the Expanded Disability Status Scale score (r = -0.5006, p = 0.0048; and r = -0.5040, p = 0.0045, respectively) and Multiple Sclerosis Severity Score (r = -0.4682, p = 0.0091; and r = -0.4706, p = 0.0087, respectively), but not with age at disease onset, disease duration, or annualized relapse rate. In HCs, the percentages of Vδ2+ and Vδ2+Vγ9+ cells of total CD3+ T cells had strong positive correlations with the percentage of CD25+CD127low/- cells in CD4+ T cells (r = 0.7826, p < 0.0001; and r = 0.7848, p < 0.0001, respectively), whereas such correlations were totally absent in MS patients. These findings suggest that decreased Vδ2+Vγ9+ γδ T cells are associated with disability in MS. Therefore, the Vδ1/Vδ2 ratio might be a candidate biomarker for predicting disease severity in MS.

Dataset Information

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease.

Publications

Decreased levels of regulatory B cells in patients with acute pancreatitis: association with the severity of the disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets