ROLE OF ANTIGEN SELECTIVITY IN AUTOIMMUNE RESPONSES TO THE KU-(P70/P80) ANTIGEN
ROLE OF ANTIGEN SELECTIVITY IN AUTOIMMUNE RESPONSES TO THE KU-(P70/P80) ANTIGEN
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DOI：
10.1172/jci114199
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发表时间：
1989-08-01
影响因子：
15.9
通讯作者：
LAHITA, RG
中科院分区：
文献类型：
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作者：
REEVES, WH;STHOEGER, ZM;LAHITA, RG
抗Ku（p70/p80）抗体水平纵向测量血清中的4个人与系统性红斑狼疮或相关疾病。天然Ku抗原（p70/p80复合物）的抗体变化范围高达577倍。在Ku（p70/p80）抗原的几个不同表位的自身抗体水平也观察到大的波动。这些个体自身抗体群体的水平通常彼此重叠，表明它们是协调调节的。在某些血清中也观察到类似的抗DNA抗体波动模式。为了检查这些自身抗体由多克隆B细胞活化产生的可能性，将抗Ku（p70/p80）和抗DNA抗体的水平与大肠杆菌蛋白、破伤风类毒素和牛胰岛素、转铁蛋白、细胞色素c、血清白蛋白和甲状腺球蛋白的抗体水平进行比较。在来自同一个体的血清中，抗Ku（p70/p80）抗体有时在完全不存在多克隆活化的情况下产生，而在其他时间伴随着多克隆活化的增加。抗DNA抗体水平比抗Ku（p70/p80）水平更接近多克隆活化水平。这些研究表明，抗Ku（p70/p80）抗体产生的抗原选择性机制，但多克隆激活频繁，虽然不是一成不变的，伴随着自身抗体的生产。该观察结果与多克隆活化与多克隆活化可能继发于自身抗体产生的可能性一致。
Levels of anti-Ku (p70/p80) antibodies were measured longitudinally in sera from four individuals with systemic lupus erythematosus or related disorders. Antibodies to the native Ku antigen (p70/p80 complex) varied over a range of up to 577-fold. Large fluctuations were also observed in the levels of autoantibodies to several distinct epitopes of the Ku (p70/p80) antigen. Levels of these individual autoantibody populations generally paralleled one another, suggesting that they are coordinately regulated. A similar pattern of anti-DNA antibody fluctuation was seen in some sera. To examine the possibility that these autoantibodies were generated by polyclonal B cell activation, the levels of anti-Ku (p70/p80) and anti-DNA antibodies were compared to the levels of antibodies to Escherichia coli proteins, tetanus toxoid, and bovine insulin, transferrin, cytochrome c, serum albumin, and thyroglobulin. In sera from the same individual, anti-Ku (p70/p80) antibodies were sometimes produced in the complete absence of polyclonal activation and at other times were accompanied by increased polyclonal activation. Anti-DNA antibody levels more closely paralleled the level of polyclonal activation than did the anti-Ku (p70/p80) levels. These studies suggest that anti-Ku (p70/p80) antibodies are generated by an antigen-selective mechanism, but that polyclonal activation frequently, although not invariably, accompanies autoantibody production. This observation is consistent with the possibility that polyclonal activation is consistent with the possibility that polyclonal activation might be secondary to autoantibody production.