Study of MicroRNA-122 as a Diagnostic Biomarker of Sepsis.

Sepsis in intensive care units (ICUs) represent a threat with need for rapid and accurate diagnosis. We aimed to assess miR-122 as an early biomarker for diagnosis and outcome prediction in patients with hospital acquired sepsis in ICU. This case control study included 25 adults' patients with sepsis and 25 patients with local wound infections as a control group. C-reactive protein (CRP), total leucocytes count (TLC), liver function, and molecular determination of miR-122 levels were assessed. miR-122 had significant higher area under curve (AUC) when compared with CRP and TLC for differentiation of sepsis from wound infections. The cut off value for miR-122 was 0.16 folds expression with sensitivity, specificity and accuracy 100%. The TLC cut off value was 14.00 x103/cmm with 100% sensitivity, 84% specificity and 92% accuracy. While CRP cut off value was 41 mg/l with 76.0% sensitivity, 100% specificity, and 88.0% accuracy. Multivariate logistic analysis revealed non statistically significant difference between survivors and non survivors regarding sepsis biomarkers. Receiver operation curve (ROC) for different biomarkers, CRP, TLC and miR-122 to differentiate patients with poor outcome of sepsis compared to patients with recovery, revealed that AUC was 0.61, 0.6, and 0.45 respectively. miR-122 as a prognostic biomarker for sepsis had 66.6% sensitivity, 50% specificity, and 56.0% accuracy. The present study highlights important points in the use of biomarkers in diagnosis of sepsis in adults' patients above 50 years old. miR-122 is an accurate and specific biomarker for diagnosis of sepsis. miR-122 has limited predictive value for determination of the outcome of patients with sepsis even when used in combination with another biomarker such as CRP and TLC.

Epstein Barr Virus in Patients with Nephropathy Associated with Systemic Lupus Erythematous, Pilot Study in Egyptian Patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting young age adults especially females. Infection with Epstein Barr virus (EBV) represents a common pathogen associated with SLE activity. This study investigates the occurrence of EBV in SLE patients with renal complications by serological markers and molecular detection of EBV genome in renal biopsies and examine the association of EBV with the pathological grades in renal diseases. The study included nineteen patients with systemic lupus nephropathy and thirteen patients with non-lupus nephropathy. Renal biopsies were subjected to detection of EBV by PCR. Serum autoantibodies (anti- dsDNA, anti-Sm and anti-RNP) and EBV-IgM and IgG antibodies were detected by ELISA. The commonest autoantibody was anti- dsDNA (73.7%) followed by anti-Sm (57.8%) and anti-RNP (31.6%). The EBV-PCR revealed that 31.6% of patients with lupus nephropathy showed positive LMP1 gene expression in renal biopsies On the other hand, serological markers for EBV showed no significant difference between both groups; IgM for EBV was positive in 26.3% of patients with lupus nephropathy and 7.7% in non-lupus nephropathy, while IgG was positive in 26.3% and 15.4 % respectively. Positive LMPI-PCR was demonstrated in all (3/3) patients with severe degree of nephropathy as compared to 23.1% of patients with moderate degree of nephropathy. A significant association was found between EBV-PCR and anti-Sm, (P=0.01), anti- dsDNA (P=0.001), and IgG for EBV and anti- dsDNA (P=0.03). In conclusion, Molecular detection of EBV DNA in renal biopsies can be applied for laboratory diagnosis in SLE nephropathy. The severity of nephropathy associated with SLE seems to be aggravated by the presence of EBV. Further extended studies are required to elucidate this association.

Th17 and IL-17 as Predictors of Hepatic Inflammation in Patients with Chronic Hepatitis C Virus Infection and Treated With Direct Antiviral Therapy.

Limited data exists on the role of Th17 cells in chronic HCV infected patients, particularly with regard to hepatic inflammation and fibrosis. We aimed to investigate the relationship between circulating and intrahepatic frequency of Th17 cells and IL-17 serum level and degrees of hepatic inflammation and fibrosis in chronic HCV patients, as well as to evaluate the effect of successful anti-viral therapy on these parameters. This nested longitudinal case control study included 30 treatment-naïve chronic HCV patients and 20 healthy individuals as control. All patients were investigated for circulating Th17 cell percentage (flow cytometry) and intrahepatic Th17 cell percentage (immunohistochemistry) and serum IL-17 (ELISA) at baseline and at week 12 after discontinuation of therapy. Circulating and intrahepatic Th17 cell percentage and serum IL17 level were found to be significantly higher in chronic HCV patients when compared with controls, with significant correlation with Metavir activity score. No patients required discontinuation of therapy due to any adverse event allowing for sustained virological response at 12 weeks (SVR12) in 24 patients while the remaining six patients were considered "non-responders". Circulating Th17 cells and serum IL17 levels were significantly decreased after successful Sofosbuvir-Ribavirin therapy (P < 0.0001). The extent of liver inflammation is positively correlated with frequencies of circulating Th17 cells, and their HCV-specific IL17 secretion, and intrahepatic Th17 cells. This data may also provide the basis for the potential use of Th17 as a new marker for disease advancement of chronic hepatitis C.

Association of interferon gamma gene polymorphism and susceptibility to hepatitis C virus infection in Egyptian patients: A multicenter, family-based study.

BACKGROUND AND AIM: Polymorphisms in some genes may influence the persistence of hepatitis C virus (HCV) infection, clinical outcome, HCV replication, and liver damage. This study was conducted to investigate the role of the interferon gamma (IFN-γ) gene at (+874 T/A, -764 G/C, -179 C/A) single-nucleotide polymorphisms (SNPs) and its receptor (IFN-γR2) at (rs 2786067 A/C) SNP in the susceptibility of Egyptian families to HCV infection with high-resolution techniques. METHODS: In total, 517 Egyptian families, with 2246 subjects, were recruited to this study from the Upper and Lower Egypt governorates and were classified into three groups: 1034 patients with chronic hepatitis C virus, 108 subjects with spontaneous virus clearance (SVC), and 1104 subjects as a healthy control group. All subjects were genotyped for (+874 T/A, rs2430561, -764 G/C, rs2069707, -179 C/A, rs2069709, and rs 27860067, A/C) SNPs of the IFN-γ gene using the allelic discrimination real-time polymerase chain reaction technique and were confirmed using sequence-based typing. RESULTS: The carriage of T allele of (+874) IFN-γ is a risky allele and was significantly higher in chronic hepatitis C more than other two groups (odds ratio [OR]: 2.6646, P < 0.0002). On the other hand, the C allele of (-764, rs2069707) is a protective allele and was higher in SVC than the other two groups (OR: 0.2709, P < 0.0001). However, both (-179 C/A, rs 2069709) and (rs 27860067, A/C) SNPs are not polymorphic enough to be studied in the Egyptian population. CONCLUSIONS: HCV infection is associated with the T allele of (+874 rs2430561), while SVC of HCV is associated with the C allele of (-764, rs2069707) of the IFN-γ gene.

GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact.

To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.