Characterization of the B cell response of patients with anti-liver cytosol autoantibodies in type 2 autoimmune hepatitis
Characterization of the B cell response of patients with anti-liver cytosol autoantibodies in type 2 autoimmune hepatitis
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DOI：
10.1002/eji.200323857
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发表时间：
2003-07-01
影响因子：
5.4
通讯作者：
Alvarez, F
中科院分区：
文献类型：
--
作者：
Lapierre, P;Johanet, C;Alvarez, F
在 2 型自身免疫性肝炎 (AIH) 患者的 30% 血清中检测到抗肝细胞溶胶 1 型 (LC1) 自身抗体，并且是 10% 病例中唯一的循环自身抗体。人甲亚氨基转移酶环脱氨酶 (FTCD) 已被证明是抗 LC1 自身抗体识别的特异性肝抗原。本研究的目的是鉴定人类 FTCD 上的显性表位并分析抗原位点序列以寻找 AIH 发展的线索。覆盖人 FTCD 整个 cDNA 的重组蛋白和肽针对抗 LC1 自身抗体进行了测试。在整个蛋白质中发现了构象表位，但仅在 C 端 146 个氨基酸中发现了线性表位。发现了两组具有不同反应性的血清：69%的血清识别了人FTCD的428-434位（NTPEEKD）和440-447位（LQEGLRRA）的两个特异性线性表位；其他的仅与 395 和 528 位氨基酸之间的不连续表位发生反应。因此，FTCD 自身抗体的产生是多克隆抗原驱动的 B 细胞反应。在所有患者中都发现了针对构象或不连续表位的自身抗体，三分之二的人还识别了人类 FTCD 上的线性表位。
Anti-liver cytosol type 1 (LC1) autoantiloody is detected in 30% of sera from patients with type 2 autoimmune hepatitis (AIH), and is the only circulating autoantibody in 10% of cases. Human formiminotransferase cyclodeaminase (FTCD) has been shown to be the specific liver antigen recognized by anti-LC1 autoantibodies. The aim of this study was to identify the dominant epitope on human FTCD and to analyze antigenic-site sequences for clues on the development of AIH. Recombinant proteins and peptides covering the entire cDNA of human FTCD were tested against anti-LC1 autoantibodies. Conformational epitopes were found throughout the protein but linear epitopes were found exclusively in the C-terminal 146 amino acids. Two groups of sera with different reactivities were found: 69% of the sera recognized two specific linear epitopes at positions 428-434 (NTPEEKD) and 440-447 (LQEGLRRA) of human FTCD; others reacted only with a discontinuous epitope between the amino acids at position 395 and 528. FTCD autoantibody production is thus a polyclonal-antigen-driven B cell response. Autoantibodies against conformational or discontinuous epitopes were found in all patients and two-thirds also recognized linear epitopes on human FTCD.