IMMUNOCHEMICAL AND MOLECULAR STUDIES IN HUMAN SCLERODERMA AND TSK MICE

硬皮病是一种以纤维化为特征的主要结缔组织疾病 受影响的器官。 进行性全身性 硬化症或CREST综合征产生抗细胞内 抗原，并显示对胶原蛋白I和II的细胞免疫改变。 一种假设是硬皮病是一种自身免疫性疾病。 各种 在硬皮病中发现的免疫异常支持了以下理论， 免疫系统可能存在根本性缺陷 人类疾病的实验模型，特别是自然发生的 与明确的遗传缺陷有关的基因是重要的研究工具 对了解疾病的发病机理有很大帮助。 皮肤紧绷的小鼠出现自发性皮肤增生和肺 肺气肿综合征，表现出人类的组织病理学图片 硬皮病 此外，我们最近发现，皮肤紧绷的老鼠产生的 抗拓扑异构酶抗体，硬皮病中发现的自身抗体， 在其他人类自身免疫性疾病中。 一个长期的目标是阐明细胞和分子机制 参与激活自身反应性免疫反应，以研究其 在这种胶原蛋白紊乱的进展中， 实验模型和人类疾病。 平行研究旨在 表征杂交瘤产生的自身抗体的特异性， 编码它们的V基因和抗体的细胞来源将允许 我们来确定遗传因素在疾病中的作用。 这些研究 都青睐的事实，即疾病的发生在紧皮肤 小鼠是由于位于2号染色体上的单一突变。

Scleroderma is a major connective tissue disease characterized by fibrosis of the affected organs. Patients with either progressive systemic sclerosis or CREST syndrome develop autoantibodies to intracellular antigens and show altered cellular immunity to Collagen I and II. One hypothesis is that scleroderma is an autoimmune disease. A variety of immunological abnormalities found in scleroderma supports the theory that there may be a fundamental defect in the immune system. Experimental models of human disease, particularly naturally occurring ones, related to a well defined genetic defect are important research tools for the understanding of the pathogenesis of disease. Tight skin mice develop a spontaneous cutaneous hyperplasia and lung emphysema syndrome which exhibit the histopathological picture of human scleroderma. Furthermore, we recently showed that tight skin mice produce anti topoisomerase antibodies, autoantibodies found in scleroderma but not in other human autoimmune disease. One long term goal is to elucidate the cellular and molecular mechanisms involved in the activation of self reactive immune response to study its eventual role in the progression of this collagen disorder in both the experimental model and human disease. Parallel studies aimed to characterize the specificities of autoantibodies produced by hybridomas, the V gene encoding them and the cellular origin of antibodies will allow us to determine the role of genetic factors in the disease. These studies are favored by the fact that the occurrence of the disease in tight skin mice is due to a single mutation located on chromosome 2.