Muro Y, Sugimoto K, Himeno M, Ohashi M
Department of Dermatology, Nagoya University School of Medicine, Japan.
J Dermatol. 1992 Oct;19(10):584-91. doi: 10.1111/j.1346-8138.1992.tb03734.x.
Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often with scleroderma). From our previous analysis of the reactivity of anticentromere sera, four independent epitopes were identified on recombinant CENP-B. The anticentromere sera displayed heterogeneity in their patterns of reactivity to the four epitopes. We have investigated to what extent this heterogeneity of the target autoepitope on CENP-B accounts for the clinical diversity of anticentromere antibody (ACA)-positive patients. A major autoepitope, epitope I, was recognized by all 40 ACA-positive sera; however, the other three epitopes were recognized differently from case to case. We could not find any significant correlation between the reactivity to CENP-B autoepitopes and the clinical presentation of ACA-positive patients. There was considerable clinical diversity, even among the nine patients showing specificity for the single major autoepitope. In conclusion, we found that, although ACA-positive patients were both clinically and immunologically heterogeneous, in most respects the clinical expression appeared to be independent of the reactivity to the CENP-B autoepitope, a finding which suggests that identification of the target epitope of CENP-B is unlikely to assist in the clinical classification of the disease in ACA-positive patients. The identification of multiple B cell epitopes on CENP-B is consistent with the concept that the self-antigen drives the antibody response. However, factors other than CENP-B autoepitope specificity must determine the clinical expression of ACA responses.
着丝粒蛋白B（CENP - B）是一种α卫星DNA结合蛋白，是自身免疫性疾病患者（常患硬皮病）体内的靶抗原。根据我们之前对抗着丝粒血清反应性的分析，在重组CENP - B上鉴定出了四个独立的表位。抗着丝粒血清对这四个表位的反应模式存在异质性。我们研究了CENP - B上靶自身表位的这种异质性在多大程度上导致了抗着丝粒抗体（ACA）阳性患者的临床多样性。一个主要的自身表位，即表位I，被所有40份ACA阳性血清识别；然而，其他三个表位的识别情况则因病例而异。我们未发现对CENP - B自身表位的反应性与ACA阳性患者临床表现之间存在任何显著相关性。即使在对单一主要自身表位具有特异性的九名患者中，临床多样性也相当大。总之，我们发现，尽管ACA阳性患者在临床和免疫学上均具有异质性，但在大多数方面，临床表型似乎与对CENP - B自身表位的反应性无关，这一发现表明，鉴定CENP - B的靶表位不太可能有助于对ACA阳性患者进行疾病的临床分类。在CENP - B上鉴定出多个B细胞表位与自身抗原驱动抗体反应这一概念相符。然而，除CENP - B自身表位特异性之外的因素必定决定了ACA反应的临床表型。
