Serum profile of T helper 1 and T helper 2 cytokines in hepatitis C virus infected patients.

BACKGROUND: T-helper (Th) lymphocyte cytokine production may be important in the immune pathogenesis of hepatitis C virus (HCV) infections. Th1 cytokines such as; interleukin-2 (IL-2), and interferon gamma (IFN-gamma) are necessary for host antiviral immune responses, while Th2 cytokines (IL-4, IL-10) can inhibit the development of these effector mechanisms. OBJECTIVES: The aim of the present study was to assess the serum profile of Th1 and Th2 cytokines in treated and non-treated HCV infected individuals. PATIENTS AND METHODS: This study was carried out in 63 HCV infected patients (31 under treatment and 32 untreated) and 32 matched HCV-sero negative healthy subjects. Serum samples were checked with an enzyme-linked immune sorbent assay (ELISA) for IL-2, IL-4, IL-10 and IFN-gamma. RESULTS: Levels of circulating IL-2, IL-4, IL-10 and IFN-gamma were significantly elevated in HCV patients versus normal controls (2 822.6 ± 1 259.92 vs. 950.8 ± 286.9 pg/mL; 1 987 ± 900.69 vs. 895.91 ± 332.33 pg/mL; 1 688.5 ± 1 405.1 vs. 519.03 ± 177.64 pg/mL and 1 501.9 ± 1 298 vs. 264.66 ± 71.59 pg/mL, respectively; P < 0.001). The serum levels of all cytokines were significantly lower in the patients under treatment than those of the untreated patients (P < 0.001). CONCLUSIONS: On the basis of our data, the simultaneous increase of Th1 and Th2 related cytokines may indicate that both Thl and Th2 cytokines are involved in the pathogenesis of HCV infections. Moreover, this activated T-cell response in HCV infected patients may be regulated by treatment.

In silico analysis of six known Leishmania major antigens and in vitro evaluation of specific epitopes eliciting HLA-A2 restricted CD8 T cell response.

BACKGROUND: As a potent CD8(+) T cell activator, peptide vaccine has found its way in vaccine development against intracellular infections and cancer, but not against leishmaniasis. The first step toward a peptide vaccine is epitope mapping of different proteins according to the most frequent HLA types in a population. METHODS AND FINDINGS: Six Leishmania (L.) major-related candidate antigens (CPB,CPC,LmsTI-1,TSA,LeIF and LPG-3) were screened for potential CD8(+) T cell activating 9-mer epitopes presented by HLA-A*0201 (the most frequent HLA-A allele). Online software including SYFPEITHI, BIMAS, EpiJen, Rankpep, nHLApred, NetCTL and Multipred were used. Peptides were selected only if predicted by almost all programs, according to their predictive scores. Pan-A2 presentation of selected peptides was confirmed by NetMHCPan1.1. Selected peptides were pooled in four peptide groups and the immunogenicity was evaluated by in vitro stimulation and intracellular cytokine assay of PBMCs from HLA-A2(+) individuals recovered from L. major. HLA-A2(-) individuals recovered from L. major and HLA-A2(+) healthy donors were included as control groups. Individual response of HLA-A2(+) recovered volunteers as percent of CD8(+)/IFN-γ(+) T cells after in vitro stimulation against peptide pools II and IV was notably higher than that of HLA-A2(-) recovered individuals. Based on cutoff scores calculated from the response of HLA-A2(-) recovered individuals, 31.6% and 13.3% of HLA-A2(+) recovered persons responded above cutoff in pools II and IV, respectively. ELISpot and ELISA results confirmed flow cytometry analysis. The response of HLA-A2(-) recovered individuals against peptide pools I and III was detected similar and even higher than HLA-A2(+) recovered individuals. CONCLUSION: Using in silico prediction we demonstrated specific response to LmsTI-1 (pool II) and LPG-3- (pool IV) related peptides specifically presented in HLA-A*0201 context. This is among the very few reports mapping L. major epitopes for human HLA types. Studies like this will speed up polytope vaccine idea towards leishmaniasis.

Persistence of antibody to hepatitis B surface antigen among vaccinated children in a low hepatitis B virus endemic area.

BACKGROUND: A potential problem of hepatitis B immunization is that vaccine-induced antibody to hepatitis B surface antigen (anti-HBs) declines to low levels with age. This study investigated the persistence of anti-HBs in vaccinated children in a low hepatitis B virus (HBV) endemic area. METHODS: Plasma samples of 938 children between ages of 8 months and 15 years were tested for the presence of anti-HBs. RESULTS: The seroprotection rate was 60%. Protective antibody level was detected in 65% of children one year after vaccination, and in 30%, 29% and 24% 5, 10 and 15 years after vaccination, respectively. The mean anti-HBs titer declined with post-vaccination time (to 66 mIU/mL in 1 year, 60 mIU/mL in 5 years, 40 mIU/mL in 10 years to 37 mIU/mL in 15 years after vaccination). CONCLUSIONS: Children vaccinated against HBV during infancy may show low levels of antibody during adolescence. Our data suggest that a booster dose of vaccine may be required in low HBV endemic areas.

Occult hepatitis B virus infection in hemodialysis patients with isolated hepatitis B core antibody: a multicenter study.

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Occult HBV infection harbors potential risk of HBV transmission through hemodialysis (HD). The aim of this study was to assess the occult HBV infection in hemodialysis patients with isolated hepatitis B core antibody (anti-HBc). A total of 289 HD patients from five dialysis units in Tehran, Iran, were included in this study. Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (anti-HBs), anti-HBc, Hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of HD patients with isolated anti-HBc (HBsAg negative, anti-HBs negative and anti-HBc positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. Of 289 patients enrolled in this study, 18 subjects (6.2%, 95% confidence interval (CI), 3.5%-8.9%) had isolated anti-HBc. HBV-DNA was detectable in 9 of 18 patients (50%, 95% CI, 27%-73%) who had isolated anti-HBc. Plasma HBV-DNA load was less than 50 IU/ml in all of these patients. Our study showed that detection of isolated anti-HBc could reflect unrecognized occult HBV infection in HD patients. The majority of these infections are associated with low viral loads.

Seroepidemiology of hepatitis A virus in children of different age groups in Tehran, Iran: implications for health policy.

BACKGROUND: Hepatitis A is one of the most frequently reported vaccine-preventable diseases throughout the world and remains endemic in many areas. Studies in various communities have shown that Hepatitis A virus (HAV) prevalence rises with age. The current data regarding hepatitis A epidemiology in Iran is limited. The aim of this study was to determine the seroepidemiology of hepatitis A in children of different age groups in Tehran, Iran. METHODS: Plasma samples of 1065 children between ages of 6 months and 20 years were tested for the presence of total anti-HAV. The study population was stratified according to age. RESULTS: The prevalence of total anti-HAV was 61.6%. HAV prevalence rates according to age groups were as follows: 61.5% between 6 months and 1.9 years, 51.7% between 2 and 5.9 years, 52.9% between 6 and 10.9 years, 65.2% between 11 and 15.9 years, 85% between 16 and 20 years. Total anti-HAV seroprevalence was significantly different between age groups. CONCLUSION: The study findings indicate that hepatitis A is prevalent in children in Tehran, Iran and HAV infection is an important public health problem in this region.