AUTOANTIBODIES IN SCLERODERMA AND RAYNAUD'S PHENOMENON

抗着丝粒抗体（ACA）存在于患有 硬皮病、CREST、原发性或继发性雷诺现象与3 着丝粒蛋白（CENP）：CENP-A、CENP-B和CENP-C。 CENP-B 主要的自身抗原，已被克隆并在E.杆菌 抗Scl-70 与拓扑异构酶I反应。 该抗原已被克隆，此外， 化学纯化。 抗CENP-B和抗拓扑异构酶I的ELISA 已经建立，比免疫印迹法更敏感， 免疫扩散 抗拓扑异构酶I可预测紧 皮肤和抗CENP-B的毛细血管扩张症患者的发展 原发性雷诺病 我们发现伊加和IgM抗拓扑异构酶I 和ACA。 将使用ELISA和免疫印迹法研究自身抗体。 CENP-C和CENP-A将在细菌中完全克隆和表达。 的 将对拓扑异构酶I、CENP-C和CENP-A上的表位进行定位，以确定 自身抗体反应是否是多克隆的， 抗CENP-B抗体。 将研究抗拓扑异构酶反应， 确定免疫球蛋白的类别和亚类，并确定是否有 是如抗CENP-B应答所发现的重链或轻链偏斜。 的 伊加、IgM型ACA和抗拓扑异构酶I检测的临床意义 将在硬皮病及其亚群中研究自身抗体。 “正常” 抗拓扑异构酶I和ACA将与疾病状态中的那些进行比较。 将对雷诺氏病患者进行一项为期5年的前瞻性研究， 以确定存在的临床意义， 抗CENP-B、抗CENP-A、抗CENP-C和抗拓扑异构酶I的量。

Anticentromere antibodies (ACA) present in sera from patients with scleroderma, CREST, primary or secondary Raynaud's phenomenon react with 3 centromeric proteins (CENPs): CENP-A, CENP-B, and CENP-C. CENP-B, the major autoantigen, has been cloned and expressed in E. coli. Anti-Scl-70 reacts with topoisomerase I. The antigen has been cloned and, in addition, chemically purified. An ELISA for anti-CENP-B and for anti-Topoisomerase I have been established and are more sensitive than immunoblotting or immunodiffusion. Anti-topoisomerase I predicts the development of tight skin and anti-CENP-B the development of telangiectasias in patients with Primary Raynaud's disease. We have found IgA and IgM anti-topoisomerase I and ACA. The autoantibodies will be studied using the ELISA and immunoblotting. CENP-C and CENP-A will be fully cloned and expressed in bacteria. The epitopes on topoisomerase I, CENP-C, and CENP-A will be mapped to determine whether the autoantibody response is polyclonal as appears to be the case for anti-CENP-B. The anti-topoisomerase response will be studied to determine immunoglobulin class and subclass and to determine whether there is heavy or light chain skewing as found for the anti-CENP-B response. The clinical significance of IgA and IgM ACA and anti-topoisomerase I autoantibodies will be studied in scleroderma and its subsets. "Normal" anti-topoisomerase I and ACA will be compared with those in disease states. A prospective 5 year study of patients with Raynaud's disease will be carried out to determine the clinical significant of the presence and amount of anti-CENP-B, anti-CENP-A, anti-CENP-C, and anti-topoisomerase I.