AUTOANTIBODIES IN SCLERODERM AND RAYNAUDS PHENOMENON

抗着丝粒抗体(ACA)在慢性粒细胞白血病患者血清中的表达 硬皮病、冠部、原发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，即 主要自身抗原基因已被克隆并在大肠杆菌中表达。抗SCL-70 与拓扑异构酶I反应。该抗原已被克隆，此外， 经过化学提纯的。抗CENP-B和抗拓扑异构酶I的酶联免疫吸附试验 已经被证实，并且比免疫印迹或 免疫扩散。抗拓扑异构酶I预测紧凑型多发性硬化的发展 皮肤和抗CENP-B与毛细血管扩张的关系 原发雷诺氏病。我们发现了抗拓扑异构酶I的IgA和IgM 和ACA。 将使用ELISA法和免疫印迹法对自身抗体进行研究。 CENP-C和CENP-A将被完全克隆并在细菌中表达。这个 将绘制拓扑异构酶I、CENP-C和CENP-A的表位图，以确定 自身抗体反应是否像看起来那样是多克隆的？ 用于抗CENP-B。抗拓扑异构酶反应将被研究到 确定免疫球蛋白类别和亚类，并确定是否有 在抗CENP-B反应中发现重链或轻链偏斜。这个 IgA、IgM、ACA和抗拓扑异构酶I检测的临床意义 自身抗体将在硬皮病及其亚型中进行研究。“正常” 抗拓扑异构酶I和ACA将与疾病状态下的进行比较。 一项对雷诺氏病患者的前瞻性5年研究将是 以确定存在和存在的临床意义 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.