Cho H, etal., Gut Liver. 2016 Mar;10(2):288-94. doi: 10.5009/gnl14368.
BACKGROUND/AIMS: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic he
patitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). METHODS: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. RESULTS: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. CONCLUSIONS: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.
Yoon H, etal., Gut Liver. 2017 Jan 15;11(1):79-86. doi: 10.5009/gnl15585.
BACKGROUND/AIMS: To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis after Helicobacter pylori (HP) infection and after HP eradication. METHODS: We divided non-cancer patients into four groups according to the status of H
P infection and atrophic gastritis (AG)/intestinal metaplasia (IM). We compared cIAP2 mRNA expression among these four groups and patients with HP-positive early gastric cancer (EGC) by using real-time polymerase chain reaction (PCR). We evaluated the expression of cIAP2 messenger RNA (mRNA)/protein by using real-time PCR/immunohistochemistry and the degree of apoptosis with a terminal deoxynucleotidyl transferasemediated nick end labeling assay before and 12 months after endoscopic submucosal dissection (ESD) in HP-positive EGC patients, regardless of whether they had undergone eradication therapy. RESULTS: The expression of cIAP2 mRNA was significantly higher in the groups with HP(+), AG/IM(+), and HP-positive EGC than in the control, HP(+), and AG/ IM(-) groups (p<0.005). In the HP eradication group, the expression of cIAP2 mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12-month follow-up after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period. CONCLUSIONS: The expression of cIAP2 increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression of cIAP2 and suppressed cell apoptosis.
Lee C, etal., Gut Liver. 2017 Nov 15;11(6):789-797. doi: 10.5009/gnl16454.
Background/Aims: Gastric cancer evolves in the pathologic mucosal milieu, and its development is characterized by both the loss of acid-secreting parietal cells and mucosal cell metaplasia, called spasmolytic polypeptide-expressing metaplasia (SPEM). Cytokines, such as interleukin (IL)-10
, IL-1β, and IL-6, play a key role in gastric carcinogenesis. However, changes in the cytokine profile of SPEM have not been evaluated. Methods: To induce SPEM in mouse stomachs, C57BL/6 mice were intraperitoneally injected with tamoxifen and sacrificed at 3, 10, and 21 days after treatment. RNA-sequencing (RNA-seq) and a multiplex bead array were used to measure cytokines in the stomachs of tamoxifen-treated/control mice. Results: The administration of tamoxifen led to the rapid development and histological normalization of SPEM 3 and 10 days after administration, respectively. RNA-seq revealed that the expression of IL-10 was decreased 3 days after tamoxifen administration. The multiplex assay identified a significant decline in IL-10 levels 3 days after tamoxifen treatment (58.38±34.44 pg/mL vs 94.09±4.98 pg/mL, p=0.031), which normalized at 10 and 21 days after tamoxifen treatment. Immunofluorescence staining confirmed that IL-10 expression was markedly decreased at the time of SPEM development and subsequently returned to normal, accompanied by a reversal in histologic changes. Conclusions: IL-10 may play a pivotal role in the tamoxifen-induced acute development of gastric SPEM.
Abdel-Razik A, etal., Gut Liver. 2016 Jul 15;10(4):624-31. doi: 10.5009/gnl15120.
BACKGROUND/AIMS: The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a polymorphonuclear leukocytes (PMNs) exceeding 250/μL in ascitic fluid. The aim of the study was to evaluate serum procalcitonin and ascitic fluid calprotectin as accurate diagnostic markers for detecti
ng SBP. METHODS: Seventy-nine patients with cirrhotic ascites were included. They were divided into a SBP group, including 52 patients, and a non-SBP group of 27 patients. Serum procalcitonin, ascitic calprotectin, and serum and ascitic levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL- 6) were measured using an enzyme-linked immunosorbent assay. RESULTS: Serum procalcitonin and ascitic calprotectin were significantly higher in SBP patients than in non-SBP patients. Significant increases in both serum and ascitic levels of TNF-α and IL-6 were observed in SBP patients versus non- SBP patients. At a cutoff value of 0.94 ng/mL, serum procalcitonin had 94.3% sensitivity and 91.8% specificity for detecting SBP. In addition, at a cutoff value of 445 ng/mL, ascitic calprotectin had 95.4% sensitivity and 85.2% specificity for detecting SBP. Both were positively correlated with ascitic fluid proteins, PMN count, TNF-α, and IL-6. CONCLUSIONS: According to our findings, determination of serum procalcitonin levels and ascitic calprotectin appears to provide satisfactory diagnostic markers for the diagnosis of SBP.
