Anti-histone antibodies in idiopathic and drug-induced lupus recognize distinct intrahistone regions.
Anti-histone antibodies in idiopathic and drug-induced lupus recognize distinct intrahistone regions.
复制标题
特发性狼疮和药物诱导狼疮中的抗组蛋白抗体可识别不同的组蛋白内区域。
作者：
J. Portanova;R. Arndt;E. Tan;B. Kotzin
我们已经鉴定出核心组蛋白内对系统性红斑狼疮 (SLE) 和药物性狼疮中的自身抗体具有抗原性的区域。使用免疫印迹技术来确定狼疮抗体对完整组蛋白和缺乏通常暴露在天然核小体中的氨基和羧基末端氨基酸的胰蛋白酶抗性组蛋白片段的反应性。在 SLE 中，主要的抗组蛋白反应仅限于胰蛋白酶敏感区域的表位。在 20 份对多种完整组蛋白具有强抗体活性的 SLE 血清中，有 17 份对任何相应的胰蛋白酶抗性片段表现出最小的活性。普鲁卡因酰胺 (Pr) 诱导的狼疮患者的血清中存在明显不同的反应模式，其中针对 H2A、H2B 和 H2A-H2B 复合物的抗体具有很强的片段活性。有趣的是，在少数含有 H2A-H2B 复合物抗体的 SLE 血清中也发现了胰蛋白酶抗性片段的识别。与 SLE 和 Pr 诱导的狼疮不同，肼屈嗪 (Hy) 诱导的抗体主要与 H3 和 H4 发生反应。此外，这些抗体同样良好地结合到相应的胰蛋白酶抗性区域，这些抗性区域被认为在天然核小体中相对不暴露。因此，SLE、Pr 诱导的狼疮和 Hy 诱导的狼疮中抗组蛋白抗体的特异性明显不同，但在每种疾病中，反应性似乎仅限于有限数量的组蛋白决定簇。这些数据提出了一种可能性，即天然核小体形式的自身抗原可能在 SLE 中被识别，也可能在 Pr 诱导的狼疮中被识别。相比之下，Hy 诱导针对决定簇的自身抗体的倾向通常在 SLE 或 Pr 诱导的狼疮中不被识别，这可能表明在这种疾病中存在不同的免疫原性刺激。
We have identified regions within core histones that are antigenic for autoantibodies in systemic lupus erythematosus (SLE) and drug-induced lupus. An immunoblotting technique was used to determine the reactivity of lupus antibodies for intact histones and for trypsin-resistant histone fragments that lack the amino- and carboxyl-terminal amino acids that are normally exposed in native nucleosomes. In SLE, the predominant anti-histone response was restricted to epitopes in the trypsin-sensitive regions. Of 20 SLE sera that had strong antibody activity for multiple intact histones, 17 showed minimal activity with any of the corresponding trypsin-resistant fragments. A markedly different pattern of reactivity was present in sera of patients with procainamide (Pr)-induced lupus in which antibodies to H2A, H2B, and the H2A-H2B complex had strong fragment activity. Interestingly, recognition of trypsin-resistant fragments was also noted in a small number of SLE sera that contained antibodies to the H2A-H2B complex. In contrast to both SLE and Pr-induced lupus, antibodies induced by hydralazine (Hy) reacted primarily with H3 and H4. Furthermore, these antibodies bound equally well to the corresponding trypsin-resistant regions that are thought to be relatively unexposed in native nucleosomes. Thus, the specificities of anti-histone antibodies in SLE, Pr-induced lupus, and Hy-induced lupus are markedly different, but in each disease reactivity appears to be restricted to a limited number of histone determinants. The data raise the possibility that autoantigen in the form of native nucleosomes may be recognized in SLE and possibly in Pr-induced lupus. In contrast, the propensity of Hy to induce autoantibodies to determinants usually not recognized in SLE or Pr-induced lupus may suggest a different immunogenic stimulus in this disease.