Haishen Kong

Dynamic variations in the peripheral blood lymphocyte subgroups of patients with 2009 pandemic H1N1 swine-origin influenza A virus infection

BackgroundNovel Influenza A (H1N1) is an acute respiratory infectious disease. Animal experiments indicated that when H1N1 virus infected early hosts, it showed strong CD4+, CD8+, and CD4+CD25+ T cell reactions. The aim of this study was to investigate the dynamic fluctuations of the peripheral blood lymphocyte subgroups in patients infected with H1N1 swine-origin influenza A virus (S-OIV).MethodsThe frequency of T cells, B cells, natural killer (NK) cells, and regulatory T cells (Treg) in 36 severe H1N1 and 40 moderate H1N1 patients were detected at different periods by flow cytometry. In parallel, serum cytokines were detected by enzyme-linked immunosorbent assay and C-reactive protein (CRP) was analyzed through an image-type automatic biochemical analyzer. In addition, 20 healthy volunteers, who were not infected with 2009 H1N1 virus, were selected as controls.ResultsThe frequency of NK cells were decreased in all cases and CD19+ B cells were increased in severe cases than those of the controls. At 1-2d from onset, the frequency of CD4+ and CD4+CD25+ T cells in moderate cases was higher than in the severe cases. Serum cytokines, specifically IL-2, IL-4, IL-6, IL-10, and IFN-γ exhibited no significant change both in the moderate and the severe cases during the whole monitoring process. In the early stage of the disease, serum CRP levels in the severe and moderate groups were significantly higher than that in the control group.ConclusionsPatients showed different lymphocyte subgroup distributions between mild and severe cases, which might affect the incidence and development of 2009 H1N1.

Changes of Costimulatory Molecule CD28 on Circulating CD8+ T Cells Correlate with Disease Pathogenesis of Chronic Hepatitis B

Costimulatory signals are critical for antiviral immunity. The aim of this study was to evaluate the change of costimulatory molecule CD28 on circulating CD8+ T cells in chronic hepatitis B patients (CHB). Seventy CHB patients and fifty-six healthy controls were included, and forty-eight CHB patients were recruited for 52 weeks of longitudinal investigation. The proportions of circulating CD8+CD28+ and CD8+CD28− subpopulations were determined by flow cytometry, and the CD8+CD28+/CD8+CD28− T cells ratio was calculated. Compared with the subpopulation in healthy controls, high proportions of CD8+CD28− subpopulation were observed in CHB patients. Similarly, the CD8+CD28+/CD8+CD28− T cells ratio was significantly decreased in CHB patients compared with healthy controls and correlated significantly with hepatitis B virus (HBV) loads. High proportions of CD8+CD28− subpopulation and low CD8+CD28+/CD8+CD28− T cells ratio were observed in hepatitis B e antigen- (HBeAg-) positive individuals as compared with that in HBeAg-negative subjects. A significant decrease in CD8+CD28− subpopulation, increase in CD8+CD28+ subpopulation, and CD8+CD28+/CD8+CD28− T cells ratio were seen in those patients who received efficient antiviral therapy. Thus, aberrant CD28 expression on circulating CD8+ T cells and the CD8+CD28+/CD8+CD28− T cells ratio reflect the dysregulation of T cell activation and are related to the pathogenesis of chronic HBV infection.

Clinical and microbiological characteristics of pyogenic liver abscess in a tertiary hospital in East China

Abstract Pyogenic liver abscess (PLA) is a potentially life-threatening disease affecting many parts of the world, especially Asia. In this study, we explored the clinical and microbiological characteristics of PLA in Chinese patients. A 5-year (2010–2014) retrospective review of medical records on all PLA patients who were admitted to a tertiary teaching hospital was performed. Among 217 PLA cases who were confirmed cultural positive, Klebsiella pneumonia (K pneumonia) was the most common pathogen (n = 165, 76.0%), followed by Escherichia coli (n = 21, 9.7%). Notably, there is a higher incidence of diabetes mellitus in patients with K pneumoniae-induced PLA (KP-PLA) than that with non-K pneumoniae-induced PLA (non-KP-PLA)(43.0% vs 21.2%, P = .005). However, it was less prevalent for concomitant hepatobiliary disease (20.0% vs 34.6%, P = .039) and history of intraabdominal trauma or surgery (13.3% vs 38.5%, P < .001) in patients with KP-PLA. Although K pneumoniae are sensitive to most common antibiotics (antibiotic resistance rates below 10%), some strains (1.2%) developed resistant to carbapenem. These results confirmed K pneumoniae as the predominant pathogen of PLA in the area in which the study was conducted. More attention should be directed toward monitoring the emergence of carbapenem-resistant K pneumoniae. KP-PLA is frequently diagnosed in patients with metabolic diseases accompanied by serious consequences, and it is therefore prudent to see that they receive sensitivity-directed antibiotic therapy.

Molecular Epidemiology and Antibiotic Resistance Profiles of Methicillin-Resistant Staphylococcus aureus Strains in a Tertiary Hospital in China

Analysis of the genotypic characteristics and antimicrobial susceptibility patterns of methicillin-resistant Staphylococcus aureus (MRSA) is essential for the control and treatment of diseases caused by this important pathogen. In this study, MRSA isolates obtained from a tertiary caret hospital in China were subjected to spa typing, SCCmec typing, multiple locus sequence typing (MLST), and PCR targeting of the genes encoding Panton-Valentine leukocidin (PVL). The disk diffusion method was used to test the antimicrobial susceptibility of the isolates to 10 non-beta-lactam antibiotics. Among the 120 MRSA isolates studied, 18 spa types and 15 ST types were identified. The spa t311 type was the most common (a total of 60 isolates; 50%) among the study strains, and nearly all the t311 strains belonged to ST5, which is the most common ST type that was previously reported from China among the t002 isolates. ST5-II/t311 was the major prevalent clone (55, 45.8%), which was followed by ST5-II/t002 (12, 10.0%) and ST59-IV/t437 (11, 9.2%). PVL-encoding genes were found in 6.7% of the isolates. Although the ST5-II/t311 and ST5-II/t002 clones are different spa types, they shared the same resistance profile (clindamycin, erythromycin, and ciprofloxacin). Most isolates of the ST239-III/t037 clone were resistant to clindamycin, erythromycin, ciprofloxacin, gentamicin, tetracycline, and trimethoprim/sulfamethoxazole. By contrast, the MRSA isolates of the ST239-III/t030 clone were more resistant to rifampin, but they were susceptible to trimethoprim/sulfamethoxazole. Our data emphasize the need for ongoing epidemiologic surveillance.

Increasing LAG-3 expression suppresses T-cell function in chronic hepatitis B: A balance between immunity strength and liver injury extent

Abstract Weak or absent virus-specific CD8+ T-cell responses to hepatitis B virus (HBV) infection are thought to be responsible for persistent HBV infection. Previous studies have indicated that multiple inhibitory receptors, including lymphocyte activation gene-3 (LAG-3), can suppress the CD8+ T-cell response in chronic viral infection. This study aimed to detect LAG-3 expression and to investigate the manner in which the immune response is regulated to balance the strength of the response with the extent of liver injury in chronic HBV infection. The results showed that LAG-3 expression levels were significantly higher in CD8+ T cells from chronic hepatitis B patients in the immune-active phase compared with chronic asymptomatic HBV carriers and healthy controls. CD8+ T-cell function was suppressed in cells with high LAG-3 expression, and these cells exhibited reduced interferon-&ggr; (IFN-&ggr;) secretion. Furthermore, IFN-&ggr; secretion was restored in CD8+ T cells that were treated with a specific antibody to LAG-3. Taken together, liver injury was prominent in the immune-active phase, but suppressing T-cell function could mitigate this damage. Importantly, the inhibitory function of LAG-3 can be blocked using a LAG-3-specific antibody, and this can restore the activity of non-functional T cells.

Inhibition of SATB1 expression in regulatory T cells contributes to hepatitis B virus-related chronic liver inflammation

Regulatory T cells (Tregs) contribute to the pathogenesis of chronic hepatitis B (CHB). Special AT-rich sequence-binding protein 1 (SATB1) may be a key component of this process. In the present study, Tregs and conventional T cells (Tconvs) were isolated by magnetic cell sorting of peripheral blood from CHB patients (n=57), individuals with resolved hepatitis B virus (HBV) infections (n=15), and healthy controls (n=29). SATB1 expression was studied by reverse transcription-quantitative PCR, flow cytometry and immunofluorescence microscopy, and the correlation of SATB1 expression to the expression of liver inflammation serum markers and the HBV DNA load was assessed. CHB patients showed significantly reduced SATB1 expression in Tregs than healthy controls and individuals with resolved HBV infections. Moreover, SATB1 expression in Tregs was significantly lower than in Tconvs of patients with chronic HBV infection. Serum HBV DNA and liver inflammation markers were inversely correlated to the SATB1 mRNA level in Tregs. Antiviral treatment was accompanied by increased expression of the SATB1 gene in Tregs. Thus, Tregs from CHB patients have reduced levels of SATB1, which is resolved with antiviral therapy. Inhibition of SATB1 expression may impair the hepatic inflammatory response and contribute to HBV persistence.