Induction of IgA and sustained deficiency of cell proliferative response in chronic hepatitis C

World J Gastroenterol. 2008 Nov 28;14(44):6844-52. doi: 10.3748/wjg.14.6844.

Abstract

Aim: In the present study, antibody and peripheral blood mononuclear cells (PBMC) proliferative responses against hepatitis C virus (HCV) antigens were evaluated in HCV chronically infected patients.

Methods: Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay (ELISA) and carboxyfluorescein succinimidyl ester staining.

Results: Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM (P = 0.027) and IgG (P = 0.0006) was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid (P = 0.017) and NS3 (P = 0.005) after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage (P = 0.036). IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4+ or CD8+ T cells, being the capsid poorly recognized.

Conclusion: These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibody Formation
  • Antiviral Agents / therapeutic use
  • Capsid Proteins / immunology
  • Cell Proliferation* / drug effects
  • Female
  • Hepacivirus / drug effects
  • Hepacivirus / immunology*
  • Hepatitis C Antibodies / blood*
  • Hepatitis C Antigens / immunology*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Immunoglobulin A / blood*
  • Interferon-alpha / therapeutic use
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Ribavirin / therapeutic use
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Up-Regulation
  • Viral Envelope Proteins / immunology
  • Viral Nonstructural Proteins / immunology

Substances

  • Antiviral Agents
  • Capsid Proteins
  • E1 protein, Hepatitis C virus
  • Hepatitis C Antibodies
  • Hepatitis C Antigens
  • Immunoglobulin A
  • Interferon-alpha
  • NS3 protein, hepatitis C virus
  • Viral Envelope Proteins
  • Viral Nonstructural Proteins
  • Ribavirin