Increased Circulating CD4+CD25+CD127low/neg Regulatory T-cells as a Prognostic Biomarker in Acute Pancreatitis

Minkov, G.; Yovtchev, Yovcho; Halacheva, Krasimira

doi:10.1097/mpa.0000000000000894

Cited by 14 publications

(14 citation statements)

References 37 publications

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“…In the present study, we found that the levels of CD4 + Foxp3 and Tregs population were significantly increased with positive correlation with the blood levels of ET, TNF-α, and IL-1β in SAP rats. The finding is inconsistent with some studies ( Ding et al, 2007 ; Pan et al, 2017 ), but is supported by others ( Xiong et al, 2012 ; Minkov et al, 2017 ). Our results indicated that the Tregs were activated under inflammatory condition and intestinal mucosal immunity was shifted from an over-inflammatory state to an immunosuppressed state in ASP rats.…”

Section: Discussioncontrasting

confidence: 71%

“…Studies have shown that Tregs were decreased and negatively correlated with serum concentration of TNF-α and the decrease of Tregs may be responsible for uncontrolled immune activation to cause excessive inflammatory response in SAP ( Ding et al, 2007 ; Pan et al, 2017 ). However, another study has showed that the Tregs are abnormal high in SAP patients and elevated circulating Tregs is an independent prognostic biomarker for patients with ASP ( Minkov et al, 2017 ). In the present study, we found that the levels of CD4 + Foxp3 and Tregs population were significantly increased with positive correlation with the blood levels of ET, TNF-α, and IL-1β in SAP rats.…”

Section: Discussionmentioning

confidence: 99%

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Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

et al. 2018

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Intestinal mucosal immune barrier dysfunction plays a key role in the pathogenesis of severe acute pancreatitis (SAP). Rhubarb is a commonly used traditional Chinese medicine as a laxative in China. It markedly protects pancreatic acinar cells from trypsin-induced injury in rats. Free total rhubarb anthraquinones (FTRAs) isolated and extracted from rhubarb display the beneficial effects of antibacteria, anti-inflammation, antivirus, and anticancer. The principal aim of the present study was to investigate the effects of FTRAs on the protection of intestinal injury and modification of the intestinal barrier function through regulation of intestinal immune function in rats with SAP. We established a rat model of SAP by injecting 3.5% sodium taurocholate (STC, 350 mg/kg) into the biliopancreatic duct via retrograde injection and treated the rats with FTRAs (36 or 72 mg/kg) or normal saline (control) immediately and 12 h after STC injection. Then, we evaluated the protective effect of FTRAs on intestinal injury by pathological analysis and determined the levels of endotoxin (ET), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), nitric oxide (NO), myeloperoxidase (MPO), capillary permeability, nucleotide-binding oligomerization domain-like receptors 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC), casepase-1, secretary immunoglobulin A (SIgA), regulatory T cells (Tregs), and the ratio of Th1/Th2 in the blood and/or small intestinal tissues or mesenteric lymph node (MLN) cells. Moreover, the chemical profile of FTRAs was analyzed by HPLC-UV chromatogram. The results showed that FTRAs significantly protected intestinal damage and decreased the levels of ET, IL-1β, TNF-α, and NO in the blood and TNF-α, IL-1β, and protein extravasation in the intestinal tissues in SAP rats. Furthermore, FTRAs significantly decreased the expressions of NLRP3, ASC, and caspase-1, the number of Tregs and the ratio of Th1/Th2, while significantly increased the expression of SIgA in the intestinal tissues and/or MLN cells in SAP rats. Our results indicate that FTRAs could protect intestinal injury and improve intestinal mucosal barrier function through regulating immune function of SAP rats. Therefore, FTRAs may have the potential to be developed as the novel agent for the treatment of SAP clinically.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

et al. 2018

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“…It has been indicated that >90% of Tregs with low expression of CD127 are found to express FoxP3, showing a negative correlati'on between CD127 dim+ and FoxP3 + . 15,16 On the other hand, CD127 is much more convenient to detect. Therefore, the phenotype of CD4 + CD25 str+ CD127 dim+ was used instead of CD4 + CD25 str+ FoxP3 + to identify CD4 + Tregs in our present study.…”

Section: Discussionmentioning

confidence: 99%

The predictive value of regulatory T cells on glucocorticoid sensitivity in patients with immune thrombocytopenia: a multicentre, prospective clinical study

Zhao

Tong

et al. 2021

Br J Haematol

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Glucocorticoids (GC) are used as the first-line treatment of immune thrombocytopenia (ITP), but 10-20% of patients are insensitive to them. Regulatory T cells (Tregs) can maintain immune tolerance in autoimmune diseases. The present research pooled 55 patients with newly diagnosed ITP and 44 healthy volunteers from seven hospitals. All patients received GC treatment and were divided into GC-sensitive and GC-insensitive groups according to the curative effect after 2 weeks of treatment. The levels of lymphocyte subgroups and Tregs were recorded. As the results indicated, the levels of CD8 + CD25 str+ Tregs in the GC-sensitive group were significantly higher than that of the GC-insensitive group (P = 0Á005). The optimal critical value of CD8 + CD25 str+ Tregs to distinguish GC sensitivity was 0Á09%. With GC therapy the level of CD45RO + /CD8 + CD25 str+ Tregs (activated type) decreased after treatment (P = 0Á02) and the level of CD45RO À /CD8 + CD25 str+ Tregs (initial type) increased slightly (P = 0Á11). There were no obvious changes in the level of CD4 + Tregs. These findings support that the level of CD8 + CD25 str+ Tregs and its subgroups have a predictive value in judging the sensitivity to GC among patients with ITP.Trial registration: www.chictr.org.cn; ChiCTR-OON-17014165.

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“…There is evidence to support a shifting balance between the systemic pro-inflammatory response and the compensatory anti-inflammatory response over the early course of AP 13, 29 . It was considered that the pro-inflammatory response occurs in the first few days to weeks and that the compensatory anti-inflammatory response occurs later.…”

Section: Discussionmentioning

confidence: 99%

Immune enhancement to prevent infected pancreatic necrosis: A double-blind randomized controlled trial

Zhou

Mao

et al. 2021

Preprint

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BACKGROUND&AIMS Infected pancreatic necrosis (IPN) is a highly morbid complication of acute pancreatitis(AP). Since there is evidence of immunosuppression in the early phase of AP, immune enhancement using Thymosin alpha 1 (Tα1), which stimulates both innate and adaptive immunity, may be a therapeutic strategy to prevent IPN. Our aim was to assess the efficacy of early Tα1 treatment on the development of IPN. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial in patients with predicted severe acute necrotizing pancreatitis (ANP). ANP patients with an APACHE II score≥8 admitted within seven days of the advent of symptoms were considered eligible. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg, every 12 hours for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebo (normal saline). The primary outcome was the development of IPN during the index admission. RESULTS From Mar 2017 through Dec 2020, 508 patients were randomized at 16 hospitals, of whom 254 were assigned to receive Tα1 and 254 placebo. During the index admission, 40/254 (15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95%CI -7.4% to 5.0%]; p=0.47). The results were similar in four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15.0%; p=0.15), bleeding (6.3% vs. 3.5%; p=0.15), and gastrointestinal fistula (2.0% vs. 2.4%; p=0.75) during the index admission. CONCLUSIONS The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.

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Increased Circulating CD4+CD25+CD127low/neg Regulatory T-cells as a Prognostic Biomarker in Acute Pancreatitis

Abstract: The percentage of circulating Tregs may be implicated in the development of early immune suppression in AP. Elevated percentage of circulating Tregs at admission in AP is an independent prognostic biomarker for severe disease.

Cited by 14 publications

References 37 publications

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

The predictive value of regulatory T cells on glucocorticoid sensitivity in patients with immune thrombocytopenia: a multicentre, prospective clinical study

Immune enhancement to prevent infected pancreatic necrosis: A double-blind randomized controlled trial

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