Intensity of HLA-A2 Expression Significantly Decreased in Occult Hepatitis B Infection.

BACKGROUND: Occult hepatitis B infected (OBI) patients cannot eradicate hepatitis B virus (HBV)-DNA from their liver and peripheral blood, completely. OBJECTIVES: The main aim of this study was to investigate the rate of HLA-A2 expression on peripheral blood mononuclear cells (PBMCs) of patients with OBI. MATERIALS AND METHODS: In this experimental study, intensity of HLA-A2 was measured on the PBMCs of 57 OBI patients and 100 HBsAg-/anti-HBc+/HBV-DNA samples were enrolled as controls; measurements were performed using the flow cytometry technique. RESULTS: Flow cytometric analysis indicated that 19 (33.3%) OBI patients and 28 (28%) controls expressed HLA-A2 antigen on their PBMCs. There was no significant difference between the two groups regarding the rate of individuals expressing HLA-A2 antigen. Statistical analyses showed that the intensity of HLA-A2 expression significantly decreased in OBI patients (3.58 ± 0.1) in comparison to healthy controls (4.21 ± 0.25; P < 0.001). CONCLUSIONS: According to these results it can be concluded that decreased intensity of HLA-A2 on the PBMCs of OBI patients may lead to resistance of HBV in the patients.

CCR5 on the NK Cells and its Ligand (RANTES) Expressions are Disrupted in South-Eastern Iranian Patients With Chronic Hepatitis B Infection.

BACKGROUND: CCR5 is a receptor for CCL3 (MIP-1 α), CCL4 (MIP-1 α) and CCL5 (regulated on activation normal T cell expressed and secreted (RANTES)) and play important roles in recruitment of NK cells to the HBV infected liver. OBJECTIVES: The main purpose of this study was to investigate the expression levels of CCR5 on the NK cells and also serum levels of RANTES in chronic HBV infected (CHI) patients. MATERIALS AND METHODS: In this descriptive study 63 CHI patients and 96 healthy controls were evaluated regarding CCR5 expression on the NK cells and serum levels of RANTES using flow cytometry and ELISA techniques, respectively. Real-Time PCR technique also was used for HBV-DNA quantification. RESULTS: The results revealed that CCR5 expressing NK cells and serum levels of RANTES were decreased significantly in the CHI patients in compare to healthy control. CONCLUSIONS: Based on the results it can be concluded that NK cells of Iranian CHI patients are unable to express adequate levels of CCR5 and expression levels of RANTES by immune cells also are defected in CHI patients, hence, the migration of NK cells to the infected hepatocytes and HBV eradication from the cells is interrupted.

Downregulation of CCR5 expression on the peripheral blood CD8+ T cells of southeastern Iranian patients with chronic hepatitis B infection.

Studies indicated that CC receptor 5 (CCR5), as a receptor for CC ligand 3, CCL4, and CCL5, plays important roles in the recruitment of T cytotoxic lymphocytes to the liver of chronic HBV (CHB)-infected patients. The main purpose of this study was to investigate the expression levels of CCR5 on the CD8(+) T lymphocytes of CHB patients. This clinical study was performed on 63 CHB patients and 96 healthy controls. Flow cytometric analysis was performed to examine the expression of CCR5 on CD8(+) T cells of CHB patients. Real-time PCR was also used for HBV-DNA quantification. The results of our study demonstrated that CCR5 expressing T cytotoxic cells were decreased significantly in CHB patients in comparison to healthy control. Based on our results, it can be concluded that the percent of CCR5(+)/CD8(+) T cells in Iranian CHB patients is significantly decreased, hence their migration to the infected liver, and HBV eradication from the hepatocytes is disrupted.

T helper and B cell escape mutations within the HBc gene in patients with asymptomatic HBV infection: a study from the South-Eastern region of Iran.

BACKGROUND: Escape mutations potentially allow viruses to avoid detection and clearance by the host immune system and may represent a mechanism through which infections may persist in some patients. The association of the mutations in the HBcAg gene with Hepatitis B asymptomatic carriers (ASC) has not been studied adequately. The current study was aimed to investigate HBcAg18-27 CTL epitope mutations in ASC patients in the South-Eastern region of Iran. METHODS: 100 ASC patients were selected for this study and screened for HLA-A2 using flow cytometry. HBV-DNA was extracted from the HLA-A2 positive patients and the HBc gene was amplified using PCR. Direct double sequencing was performed to analyse mutations in the HBc gene of HBV isolates from patients with ASC. RESULTS: Overall, 25 (25%) of individuals were HLA-A2 positive. Direct double sequencing indicated no mutations in the HBcAg18-27 epitope. However, four mutations within the T helper and three mutations within the B cell epitopes of ASC patients were identified. CONCLUSIONS: The lack of mutations within the HBcAg18-27 epitope suggests that the antigenicity of this region is not altered in HBV isolates of our patients and therefore antigen presentation would occur normally to the patient's immune system through HLA-A2. However, in the course of this study we revealed some novel mutations within the T helper and B cell epitopes that may affect the efficiencies of immune response of ASC patients against these novel HBV epitopes.