Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3
Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3
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DOI：
10.1038/nm968
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发表时间：
2004-01-01
期刊：
影响因子：
82.9
通讯作者：
Falk, RJ
中科院分区：
文献类型：
--
作者：
Pendergraft, WF;Preston, GA;Falk, RJ
目前尚不清楚自身免疫是如何以及为什么发生的。在这里，我们展示了一个以前未被认识到的，可能是一般的自身免疫机制的证据。这一新发现是偶然发现的，使用的材料来自于对蛋白酶-3（PR-3）具有特异性的抗神经细胞胞质自身抗体（ANCA）引起的炎性血管疾病患者。这些患者不仅具有自身抗原（PR-3）的抗体，而且具有从PR-3的反义DNA链翻译的肽（互补PR-3，cPR-3）或该肽的模拟物的抗体。用cPR-3的中间区域免疫小鼠，不仅产生针对cPR-3的抗体，而且产生针对免疫原的正义肽对应物PR-3的抗体。PR-3和cPR-3的人和小鼠抗体彼此结合，表明独特型关系。这些发现表明，自身免疫可以通过针对与自身抗原反义或互补的肽的免疫应答来启动，然后诱导与自身抗原交叉反应的抗独特型抗体（自身抗体）。
It remains unclear how and why autoimmunity occurs. Here we show evidence for a previously unrecognized and possibly general mechanism of autoimmunity. This new finding was discovered serendipitously using material from patients with inflammatory vascular disease caused by antineutrophil cytoplasmic autoantibodies (ANCA) with specificity for proteinase-3 (PR-3). Such patients harbor not only antibodies to the autoantigen (PR-3), but also antibodies to a peptide translated from the antisense DNA strand of PR-3 (complementary PR-3, cPR-3) or to a mimic of this peptide. Immunization of mice with the middle region of cPR-3 resulted in production of antibodies not only to cPR-3, but also to the immunogen's sense peptide counterpart, PR-3. Both human and mouse antibodies to PR-3 and cPR-3 bound to each other, indicating idiotypic relationships. These findings indicate that autoimmunity can be initiated through an immune response against a peptide that is antisense or complementary to the autoantigen, which then induces anti-idiotypic antibodies (autoantibodies) that cross-react with the autoantigen.