The Decrease of Peripheral Blood CD4+ T Cells Indicates Abdominal Compartment Syndrome in Severe Acute Pancreatitis

RESEARCH ARTICLE The Decrease of Peripheral Blood CD4+ T Cells Indicates Abdominal Compartment Syndrome in Severe Acute Pancreatitis Yao Liu1,2☯, Ling Wang2☯¤, Zhifang Cai2, Peng Zhao2, Cijun Peng2‡*, Lijin Zhao2, Chidan Wan1‡* 1 Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China, 2 Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou Province, People’s Republic of China ☯ These authors contributed equally to this work. ¤ Current address: Department of Gastroenterology, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou Province, People’s Republic of China ‡ These authors also contributed equally to this work. * (CW); (CP) Abstract Objective OPEN ACCESS Citation: Liu Y, Wang L, Cai Z, Zhao P, Peng C, Zhao L, et al. (2015) The Decrease of Peripheral Blood CD4+ T Cells Indicates Abdominal Compartment Syndrome in Severe Acute Pancreatitis. PLoS ONE 10(8): e0135768. doi:10.1371/journal.pone.0135768 Editor: Pavel Strnad, RWTH Aachen, GERMANY Received: May 13, 2015 Accepted: July 24, 2015 Published: August 19, 2015 Copyright: © 2015 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All data files are available from the Figshare database (Figshare.com; DOI: 10.6084/m9.figshare.1463358). Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. Few data are available on the role of T lymphocytes and inflammatory cytokines in abdominal compartment syndrome (ACS) in severe acute pancreatitis (SAP). We conducted a retrospective study to assess the risk factors associated with ACS in SAP. Methods A total of 76 SAP patients who were admitted within 24 hours after symptom onset in our study. There were 36 patients suffering from ACS and 40 from intra-abdominal hypertension (IAH). On the 1st, 3rd and 7th days after hospital admission, the following variables were assessed: serum value of C-reactive protein (CRP), and the proportions of peripheral CD4+ and CD8+ T lymphocytes. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and computed tomography severity index (CTSI) score were assessed on days 1 and 7 after hospitalization. Results Compared with the patients with IAH, ACS patients showed statistically higher CRP value on 7th day after hospital admission, proportions of CD4+ T cells on days 1, 3, 7 and CD4+ / CD8+ ratio on day 1 were significantly lower (P < 0.05, respectively). A CD4+ T cell proportion of 30.3% on the 1st day indicated ACS with an area under the curve (AUC) of 0.774, a sensitivity with 82.5% and specificity with 72.0%, respectively. Sensitivity / specificity for predicting ACS in SAP patients on day 1 was 70.0% / 68.0% for CD4+ / CD8+ ratio, 72.2% / 65.0% for APACHE II score. PLOS ONE | DOI:10.1371/journal.pone.0135768 August 19, 2015 1 / 11 Peripheral Blood CD4+ T Cell and ACS Conclusions The reduction of peripheral blood CD4+ T lymphocytes is associated with ACS in SAP, and may act as a potential predictor of ACS in SAP. Introduction Acute pancreatitis (AP) is a mild and self-limiting disease, and approximately 80% of AP patients recover without complications [1]. However, SAP accounts for around 20% of AP patients, and is associated with a mortality rate ranging from 36% to 50% [2–3]. Severe acute pancreatitis (SAP) is most commonly characterized by cytokine activation, pancreatic necrosis, systemic inflammatory response syndrome (SIRS), and multiple organ dysfunction syndrome (MODS) [4–5]. Prediction of AP severity and outcome is essential for timely treatment and prevention of complications, and remains need to be systematic studied. Radiological imaging procedures, multiple clinico-biochemical scores, and several biochemical markers, have been used to assess severity and outcome of AP [6–9]. Intra-abdominal hypertension (IAH) is defined as sustained increase of intra-abdominal pressure (IAP) > 12 mmHg, and abdominal compartment syndrome (ACS), a lethal complication of SAP, is defined as the combination of IAP > 20 mmHg and new-onset organ failure (OF) or acute worsening of existing OF [10]. De Waele et al. [11] found that IAP above 25 mmHg was detected in 30% of SAP patients, while IAP > 15 mmHg was found in 78% of SAP patients. In SAP patients, ACS has drawn more attention, because it has a mortality rate of 30–60% [3], and the diagnosis of ACS is difficult. The symptoms of ACS may resemble those of other complications, such as infected pancreatic necrosis, SIRS, and MODS [12]. The pathophysiology of ACS is considered to be directly associated with the pancreas inflammation, which initiates a cascade of acute peripancreatic fluid collections (APFC), capillary leakage syndrome (CLS), and paralytic ileus leading to an elevated IAP [11,13]. SAP is a critical risk factor for ACS, therefore, it is necessary to routinely monitor IAP in SAP patients according to the 2013 WSACS guidelines [10]. At present, it is suggested that the cytokine cascade from the innate immune system and the activated adaptive immune system (including CD4+ and CD8+ T lymphocytes) are essential to the development of SIRS in AP [4,14]. T lymphocytes are critical in the regulation of the adaptive immune system, and have a particular effect on innate immune system. In a mice model of AP, predominantly CD4+ T cells invaded the pancreas and infiltrated border acini [15]. Alterations of the immune systems in AP patients with IAH or even ACS should be thoroughly explored indicaed that ACS is related to higher mortality and morbidity rates compared to patients without ACS [11,13]. However, the detailed mechanism of ACS in SAP patients is still unclear. In this retrospective study, we intended to identify the role of T lymphocyte in the progression of ACS in SAP patients. Materials and Methods Patients This retrospective study involved a total of 76 patients with SAP who were admitted to our institution from December 2012 to July 2014 within 24 hours after symptom onset. The diagnostic criteria of SAP were based on the revised Atlanta classification [16]. Patients who develop persistent organ failure (POF) more than 48 hours and present one or more of the following features were included in the study: (1) an Acute Physiology and Chronic Health PLOS ONE | DOI:10.1371/journal.pone.0135768 August 19, 2015 2 / 11 Peripheral Blood CD4+ T Cell and ACS Evaluation II (APACHE II) score
8; (2) local complications, such as infected pancreatic necrosis, pancreatic abscess or pseudocyst. OF was defined as score
2 according to a modified Marshall scoring system (S1 Table) for o (...truncated)