Impaired Antigen Processing and Presentation Machinery is Associated with Immunotolerant State in Chronic Hepatitis B Virus Infection

• Published in: Journal of clinical immunology Vol. 30; no. 3; pp. 419 - 425
• Main Authors: Sukriti, Sukriti, Pati, Nirupma Trehan, Bose, Sujoy, Hissar, Syed S, Sarin, Shiv Kumar
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.05.2010; Springer US; Springer Nature B.V
• Subjects: Adolescent; Adult; Antigen presentation; Antigen Presentation - genetics; Antigen processing; ATP-Binding Cassette Sub-Family B Member 2; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; Biomedical and Life Sciences; Biomedicine; Child; Chronic infection; Cysteine Endopeptidases - biosynthesis; Cysteine Endopeptidases - genetics; Enzyme-Linked Immunosorbent Assay; g-Interferon; Gene expression; Gene Expression Regulation; hepatitis B e antigen; Hepatitis B surface antigen; Hepatitis B virus; Hepatitis B, Chronic - immunology; Hepatitis Viruses - immunology; Hepatitis Viruses - pathogenicity; Humans; Immune Evasion; Immune Tolerance; Immunology; immunotolerant and immunoactive chronic hepatitis B; Infectious Diseases; Injuries; Interferon-gamma - genetics; Interferon-gamma - metabolism; interferon-γ; Internal Medicine; Liver; Low molecular weight proteins 2 and 7; Lymphocytes T; Major histocompatibility complex; Medical Microbiology; Middle Aged; Peripheral blood mononuclear cells; Polymerase chain reaction; Reverse Transcriptase Polymerase Chain Reaction; TAP protein; transporter associated with antigen processing gene 1 and 2; Tumor necrosis factor-a; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; transporter associated with antigen processing gene 1 and 2; interferon-γ; Low molecular weight proteins 2 and 7; tumor necrosis factor-a; immunotolerant and immunoactive chronic hepatitis B
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-010-9379-4

Background and Aims The mechanism of hepatitis B virus (HBV)-specific T cell hyporesponsiveness in hepatitis Be antigen (HBeAg)-positive subjects is not well understood. Inefficient antigen processing and transport to major histocompatibility complex class I molecules, namely due to low molecular weight protein (LMP) 2 and 7 and transporter associated with antigen processing (TAP) 1 and 2 genes could be playing a role. Patients and Methods Forty patients with chronic hepatitis B (CHB) infection, hepatitis B surface antigen, and HBeAg positive; 26 with raised (Gr. I) and 14 with persistently normal ALT levels (Gr. II) and 11 healthy controls (Gr. III) were studied. Total RNA was isolated from peripheral blood mononuclear cells and mRNA expression of TAP1, TAP2, LMP2, and LMP7 genes was analyzed by semi-quantitative reverse transcriptase-polymerase chain reaction method. Gamma interferon (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were quantified by enzyme-linked immunosorbent assay (ELISA) using log-log and linear graphs, respectively. Results Group II CHB patients had significantly lower mRNA expression for TAP1 (p = 0.003) and LMP2 (p = 0.002) genes as compared to Gr. I patients. The mRNA expression of TAP2 and LMP7 genes was comparable between the groups. However, expression of TAP1 (p = 0.02), TAP2 (p = 0.035), and LMP2 (p = 0.041) was found to be significantly higher in Gr. III subjects compared to Gr. I and Gr. II patients. In Gr. I and II, the IFN-γ {s54.2{9.4-165} pg/ml), (59.5{28.5-110} pg/ml)}, and TNF-α {12.0 (8.0-23.2)},{10.8(6.2-20.8)} pg/ml levels were comparable but were significantly (p = 0.00,0.004, respectively) higher than Gr. III subjects. Conclusions Low expression of TAP1 and LMP2 suggests an important role of these genes in defective viral antigen processing in immune tolerant state of CHB patients. Higher IFN-γ and TNF-α production in CHB are probably enough to potentiate liver injury but not enough to clear the chronic HBV infection. These novel observations could pave way for new therapeutic strategies for immune restoration in CHB infected patients.