Frequency of regulatory B cells phenotypes in breast cancer patients in Egypt.

Accumulating evidence has indicated that immune regulatory cells are involved in the establishment of the anti-tumor activity, however; the role of regulatory B cells (B-regs) in breast cancer (BC) remains unclear. This study intended to assess the frequency of peripheral B-regs phenotypes in patients with BC, and to determine the relation between these phenotypes and the patient's clinicopathological characters. The expressions of the immune cell populations were analyzed by four-color flow cytometry in 40 naïve BC patients and 10 age-matched apparently healthy individuals as controls attending the department of Clinical Oncology and Nuclear Medicine at Assiut University Hospitals. The percentages of B-regs phenotypes CD19+IL10+ and CD19+CD24hiCD27+IL10+ were higher in BC patients than in the controls. The percentage of CD19+IL10+ B cells phenotype was significantly associated with the HER-2 expression levels, T, and N stages of BC. In conclusion, high percentage of B-regs phenotypes CD19+IL10+ and CD19+CD24hiCD27+IL10+ in BC patients indicates a possible role in immune suppression during the development of BC.

Plasma Levels of Interleukin-35 and its Association with Clinical Features of Breast Cancer Patients at Assiut University Hospitals.

Interleukin-35 (IL-35), is a recently identified cytokine that belongs to the IL-12 family, it is a potent anti-inflammatory and immunosuppressive cytokine which was first recognized to be produced by regulatory T cells (Tregs) cells, and recently was found to be produced by regulatory B cells (Bregs). The study aimed at determining whether plasma levels of IL-35 are associated with clinical characteristics of breast cancer (BC) patients. The study included 40 patients with breast cancer (BC), and 10 matched controls. The IL-35 cytokine was measured in plasma using ELISA. Results showed that plasma IL-35levels were significantly higher in BC than healthy controls (P˂ 0.05), and were significantly associated with BC grade 2 and HER-2 over expression level "3+", suggesting that plasma IL-35 levels may be associated with the development and progression of BC.

Epidemiological typing of multidrug-resistant Klebsiella pneumoniae, which causes paediatric ventilator-associated pneumonia in Egypt.

PURPOSE: Multidrug-resistant Klebsiella pneumoniae is a common nosocomial pathogen that plays an important role in ventilator-associated pneumonia (VAP). This study aimed to define the clonal relatedness of K. pneumoniae strains isolated from paediatric VAP in addition to those isolated from environmental samples. METHODOLOGY: This study included 19 clinical and 4 environmental K. pneumoniae isolates recovered from the paediatric intensive care unit (PICU) in Assiut University Children's Hospital. The K. pneumoniae isolates were confirmed by biotyping using API strips and subjected to antimicrobial susceptibility testing. The genes coding K1 and K2 capsular types were detected by PCR. The clonal relationships between the K. pneumoniae isolates were determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Ten resistotypes were detected among all the K. pneumoniae isolates, while PFGE identified seventeen K. pneumoniae pulsotypes. Similar PFGE patterns were found between environmental and clinical isolates and between isolates recovered from different patients, suggesting the circulation of K. pneumoniae pathogens in the PICU and the role of the environment in the spread of infection. No correlation was found between the resistotypes and pulsotypes of the K. pneumoniae isolates. PFGE showed higher discriminatory power for the typing of nosocomial K. pneumoniae [Simpson's diversity index (DI)=0.96] than resistotyping (DI=0.72). CONCLUSION: As far as we know, this is the first report of the isolation of the same multidrug-resistant (MDR) K. pneumoniae pulsotype from patients and environmental samples in the same hospital ward in Egypt. This study provides a step on the way to understanding the genotyping and epidemiology of MDR K. pneumoniae for enhanced prevention of bacterial transmission.

Association between IL28B rs12979860 single nucleotide polymorphism and the frequency of colonic Treg in chronically HCV-infected patients.

The IL28B gene is associated with spontaneous or treatment-induced HCV viral clearance. However, the mechanism by which the IL28B single nucleotide polymorphism (SNP) affects the extra-hepatic HCV immune responses and its relationship to HCV pathogenesis have not been thoroughly investigated. To examine the mechanism by which IL28B affects HCV clearance. Forty Egyptian patients with chronic HCV infection receiving an Interferon/ribavirin treatment regimen were enrolled into this study. There were two groups: non-responders (NR; n = 20) and sustained virologic responders (SVR; n = 20). The initial plasma HCV viral loads prior to treatment and IL28B genotypes were determined by quantitative RT-PCR and sequencing, respectively. Liver biopsies were examined to determine the inflammatory score and the stage of fibrosis. Colonic regulatory T cell (Treg) frequency was estimated by immunohistochemistry. No significant association between IL28B genotypes and response to therapy was identified, despite an odds ratio of 3.4 to have the TT genotype in NR compared to SVR (95 % confidence interval 0.3-35.3, p = 0.3). Patients with the TT-IL28Brs12979860 genotype (unfavorable genotype) have significantly higher frequencies of colonic Treg compared to the CT (p = 0.04) and CC (p = 0.03) genotypes. The frequency of colonic Treg cells in HCV-infected patients had a strong association with the IL-28B genotype and may have a significant impact on HCV clearance.

Effect of IL6 and IL23 on double negative T cells and anti ds-DNA in systemic lupus erythematosus patients.

Several evidences suggest that DN T cells, IL23 and IL6 play a role in the pathogenesis of SLE. This study aimed to evaluate the frequency of DN T cells in SLE patients and the relation to their activity also to assess the possible role of IL6 and IL23 on DN T cells. Thirty patients with SLE and sixteen healthy blood donor females were enrolled. There was a significant increase in DN T cells in patients than controls (P=0.001). These cells had a significant positive correlation with SLEDAI (r=0.486, P=0.006). DN T cells from SLE patient samples were expanded when stimulated in vitro with RhIL6 or RhIL23 in patients than controls. Furthermore, anti ds-DNA level was found to be increased in supernatant of PBMCs when stimulated by these cytokines in different concentrations. Our findings suggest that IL6 and IL23 may play role in SLE pathogenesis through their effect on DN T cells and anti ds-DNA.

Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis.

Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extra-hepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-α and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (Treg) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic Treg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.

Association of colonic regulatory T cells with hepatitis C virus pathogenesis and liver pathology.

BACKGROUND AND AIM: Forkhead box protein P3 (FoxP3)(+) regulatory T (Treg ) cells play a fundamental role in maintaining the balance between the tissue-damaging and protective immune response to chronic hepatitis C (CHC) infection. Herein, we investigated the frequency of Treg cells in the colon and their potential relationship to the various CHC outcomes and hepatic histopathology. METHODS: Colonic biopsies were collected from three groups with CHC: treatment naïve (TN; n = 20), non-responders (NR; n = 20), sustained virologic response (SVR; n = 20), and a fourth healthy control group (n = 10). The plasma viral loads and cytokines levels were determined by quantitative real-time polymerase chain reaction, and ELISA, respectively. Liver biopsies were examined to assess inflammatory score and fibrosis stage. Colonic Treg frequency was estimated by immunohistochemistry using confocal microscopy. RESULTS: A significant increase in the frequency of colonic Treg was found in TN, and NR groups compared with the control and SVR group. The frequency of colonic Treg , plasma interleukin (IL)-10 and IL-4 levels were significantly positively correlated with viral load and negatively correlated with METAVIR inflammatory score, and fibrosis stages. CONCLUSION: Colonic Treg cells are negatively correlated with liver inflammation and hepatitis C virus (HCV) viral load, which suggests a strong linkage between gut-derived Treg cell populations and HCV infection.