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病。 受影响的器官。进行性全身性疾病患者 硬化症或冠状综合征会产生细胞内自身抗体 并显示对I型和II型胶原蛋白细胞免疫功能的改变。 一种假设是硬皮病是一种自身免疫性疾病。各种各样的 在硬皮病中发现的免疫异常支持这样的理论 免疫系统可能存在根本性缺陷。 人类疾病的实验模型，尤其是自然发生的 一种是与明确定义的基因缺陷有关的，是重要的研究工具 以了解该病的发病机制。 紧绷皮肤的小鼠出现自发性皮肤增生和肺部 展示人类组织病理学图景的肺气肿综合征 硬皮病。此外，我们最近发现，紧绷的皮肤老鼠会产生 抗拓扑异构酶抗体，硬皮病中发现但不存在的自身抗体 在其他人类自身免疫性疾病中。 一个长期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的研究 在胶原蛋白紊乱进展过程中的最终作用 实验模型和人类疾病。平行研究旨在 鉴定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 我们要确定遗传因素在疾病中的作用。这些研究 都是因为紧致皮肤的疾病的发生 老鼠是由于位于2号染色体上的一个单一突变。

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.