Double reactivity against actin and α-actinin defines a severe form of autoimmune hepatitis type 1
Double reactivity against actin and α-actinin defines a severe form of autoimmune hepatitis type 1
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DOI：
10.1007/s10875-006-9045-z
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发表时间：
2006-11-01
影响因子：
9.1
通讯作者：
Renaudineau, Yves
中科院分区：
文献类型：
--
作者：
Gueguen, Paul;Dalekos, Georgios;Renaudineau, Yves
抗丝状肌动蛋白抗体表征自身免疫性肝炎1型（AIH-1）。最近，肌动蛋白上的α-辅肌动蛋白的结合结构域被证明是主要的表位。为了测试这种反应性，开发了抗α-辅肌动蛋白酶联免疫吸附试验，并通过Western印迹证实了阳性。21/50（42%）的AIH-1患者中发现了抗α-辅肌动蛋白抗体，而肝脏疾病对照患者中为52/401（12.9%），献血者中为6/200（6%）。66%的抗丝状抗体阳性AIH-1患者同时具有抗丝状抗体和抗α-辅肌动蛋白活性。这种特异性组合反映了临床和组织学疾病活动性、持续时间短和未接受治疗。最后，使用肌动蛋白-α-辅肌动蛋白复合物测定，证明了抗丝状肌动蛋白与肌动蛋白上的α-辅肌动蛋白结合结构域的结合，以及抗α-辅肌动蛋白与α-辅肌动蛋白的辅肌动蛋白结合结构域的结合。因此，抗丝状和抗α-辅肌动蛋白抗体的频繁组合似乎是AIH-1活性的标志。
Anti-filamentous actin antibodies characterize autoimmune hepatitis type 1 (AIH-1). Recently, the binding domain of alpha-actinin on actin was shown to be a predominant epitope. To test this reactivity, an anti-alpha-actinin enzyme-linked immunosorbent assay was developed, and positivity confirmed by Western blot. Anti-alpha-actinin antibody was found in 21/50 (42%) of AIH-1 patients, compared with 52/401 (12.9%) of liver disease control patients, and with 6/200 (6%) of blood donors. Anti-filamentous and anti-alpha-actinin activities were found specifically together in 66% of anti-filamentous-positive AIH-1 patients. This combination of specificities reflected clinical and histological disease activity, short duration and absence of treatment. Finally, using an actin-alpha-actinin complex assay, the binding of anti-filamentous actin to alpha-actinin-binding domain on actin was demonstrated, as well as that of anti-alpha-actinin on the actin-binding domain of alpha-actinin. Thus, the frequent combination of anti-filamentous and anti-alpha-actinin antibodies seems to be the hallmark of activity in AIH-1.