Fujimoto M, Hamaguchi Y, Yazawa N, Komura K, Takehara K, Sato S
Department of Regenerative Medicine, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Clin Exp Immunol. 2004 Dec;138(3):534-9. doi: 10.1111/j.1365-2249.2004.02633.x.
Heat-shock proteins are highly conserved and immunogenic proteins, which may be involved in the initiation and perpetuation of autoimmune diseases. Heat-shock protein 47 (HSP47) is expressed by collagen-secreting cells such as fibroblasts and serves as a collagen-specific molecular chaperone that plays a crucial role in collagen metabolism. Abnormal collagen accumulation and autoimmunity are characteristics of systemic sclerosis (SSc). We determined the presence and prevalence of autoantibodies to HSP47 in patients with SSc and also in tight-skin (TSK/+) mice, an animal model for SSc. Anti-HSP47 autoantibodies were present in SSc patients with a frequency of 26%, while patients with systemic lupus erythematosus, those with dermatomyositis, those with keloid and healthy subjects did not have anti-HSP47 antibodies. IgG1 and IgG2 were the major Ig isotypes of the autoantibodies. Patients positive for anti-HSP47 had a significantly shorter duration of disease than those who were negative. Anti-HSP47 autoantibodies were also positive in 79% of TSK/+ mice. Thus, autoantibodies to HSP47 were present in the sera from SSc patients as well as those from TSK mice, and may be associated with the pathogenesis of SSc.
热休克蛋白是高度保守且具有免疫原性的蛋白质，可能参与自身免疫性疾病的起始和持续过程。热休克蛋白47（HSP47）由成纤维细胞等分泌胶原蛋白的细胞表达，作为一种胶原蛋白特异性分子伴侣，在胶原蛋白代谢中起关键作用。胶原蛋白异常积聚和自身免疫是系统性硬化症（SSc）的特征。我们测定了SSc患者以及SSc动物模型紧皮（TSK/+）小鼠中抗HSP47自身抗体的存在情况和流行率。SSc患者中抗HSP47自身抗体的出现频率为26%，而系统性红斑狼疮患者、皮肌炎患者、瘢痕疙瘩患者和健康受试者均无抗HSP47抗体。IgG1和IgG2是自身抗体的主要Ig亚型。抗HSP47阳性的患者病程明显短于阴性患者。79%的TSK/+小鼠抗HSP47自身抗体也呈阳性。因此，SSc患者血清以及TSK小鼠血清中均存在抗HSP47自身抗体，且可能与SSc的发病机制有关。
