Identification of T cell epitopes on soluble liver antigen in Chinese patients with auto-immune hepatitis.

Abstract

AIM:

To identify soluble liver antigen (SLA)-specific dominant epitopes and analyse the correlation between SLA-specific T cell response and the status of the disease.

METHODS:

A cross-sectional analysis of SLA-specific T cell responses to 54 overlapping peptides covering the entire SLA sequence was performed using an interferon (IFN)-γ ELISpot assay in 31 patients with auto-immune hepatitis (AIH)-1, 15 patients with primary biliary cirrhosis, 16 hepatitis B virus, seven hepatitis C virus infection and 10 healthy subjects, in order to assess the correlation between SLA-specific T cell responses and the clinical outcome.

RESULTS:

Soluble liver antigen-specific IFN-γ responses in AIH were significantly more frequent in AIH patients (58.1%) than those in controls (6.7% in PBC, P=0.001; 4.3% in hepatitis B/C, P<0.001 and 0% in healthy subjects, P=0.0015). Among 31 AIH patients, the frequency of recognition and the magnitude of response to SLA peptides in anti-SLA antibody-positive patients were higher and stronger than those negative for anti-SLA antibodies (P=0.02 and 0.037 respectively). We further analysed T-cell restriction and found that six individual SLA peptides (4, 9, 11, 12, 41 and 44) were recognized by CD4 T cells, and the most frequently recognized peptides were peptides 12 (61.1% of participants), followed by peptide 4 and peptide 44 (55.6 and 38.9% respectively). Moreover, a positive association was found between the breadth of recognition of SLA peptides and the indices of liver damage.

CONCLUSION:

T cell response to SLA in Chinese patients with AIH is broad and associated with hepatocyte damage.

• Authors: Yan Zhao, Yonghong Zhang, Yan-min Liu, Yan Liu, Xia Feng, Hui-yu Liao, Diego Vergani, Yun Ma, Hui-ping Yan
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 31 Issue 5 Pg. 721-9 (May 2011) ISSN: 1478-3231 [Electronic] United States
• PMID: 21457445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Autoantibodies
• Autoantigens
• Biomarkers
• Epitopes, T-Lymphocyte
• HLA-DR Antigens
• HLA-DRB1 Chains
• Immunodominant Epitopes
• liver antigen LA-1
• Interferon-gamma
• Aspartate Aminotransferases

Topics

• Adult
• Aged
• Asian People
• Aspartate Aminotransferases (blood)
• Autoantibodies (blood)
• Autoantigens (immunology)
• Biomarkers (blood)
• CD4-Positive T-Lymphocytes (immunology)
• Case-Control Studies
• Cells, Cultured
• Chi-Square Distribution
• China
• Cross-Sectional Studies
• Enzyme-Linked Immunosorbent Assay
• Epitope Mapping
• Epitopes, T-Lymphocyte
• Female
• HLA-DR Antigens (immunology)
• HLA-DRB1 Chains
• Hepatitis, Autoimmune (enzymology, ethnology, immunology)
• Humans
• Immunodominant Epitopes
• Interferon-gamma (metabolism)
• Male
• Middle Aged
• Severity of Illness Index