Clinical Research Centre for Autoimmune Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
Liver Int. 2011 May;31(5):721-9. doi: 10.1111/j.1478-3231.2011.02487.x. Epub 2011 Feb 25.
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.
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.
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.
T cell response to SLA in Chinese patients with AIH is broad and associated with hepatocyte damage.
鉴定可溶性肝抗原（SLA）特异性优势表位，并分析 SLA 特异性 T 细胞反应与疾病状态之间的相关性。
采用干扰素（IFN）-γ ELISpot assay 对 31 例自身免疫性肝炎（AIH）-1 患者、15 例原发性胆汁性肝硬化（PBC）患者、16 例乙型肝炎病毒（HBV）感染患者、7 例丙型肝炎病毒（HCV）感染患者和 10 例健康对照者的 SLA 序列全长 54 个重叠肽进行 SLA 特异性 T 细胞反应的横断面分析，以评估 SLA 特异性 T 细胞反应与临床结局之间的相关性。
AIH 患者的可溶性肝抗原特异性 IFN-γ 反应明显高于对照组（PBC 为 6.7%，P=0.001；HBV/C 为 4.3%，P<0.001；健康对照者为 0%，P=0.0015）。在 31 例 AIH 患者中，抗 SLA 抗体阳性患者对 SLA 肽的识别频率和反应强度均高于抗 SLA 抗体阴性患者（分别为 P=0.02 和 0.037）。我们进一步分析 T 细胞限制，发现 6 个个体 SLA 肽（4、9、11、12、41 和 44）被 CD4 T 细胞识别，最常被识别的肽是肽 12（61.1%的参与者），其次是肽 4 和肽 44（分别为 55.6%和 38.9%）。此外，SLA 肽识别的广度与肝损伤指标呈正相关。
中国 AIH 患者对 SLA 的 T 细胞反应广泛，并与肝细胞损伤相关。
