Investigation for Autoreactive T-cell to Autoantigen in Behcet's Disease

白塞病患者复发性口腔口疮先于眼部炎症的观察提示口腔链球菌在该疾病的病因学中所起的作用。热处理的链球菌抗原可引起白塞病患者的眼部炎症或全身症状。此外，在这些患者的血清中还检测到了抗视黄热休克蛋白60(HSP60)的自身抗体。注射提取的视网膜热休克蛋白60也可诱发实验性葡萄膜炎。用分子生物学方法对化脓链霉菌的视网膜HSP60和HSP60的特性进行了研究。通过聚合酶链式反应从牛视网膜cDNA文库和化脓性链球菌DNA中分离到HSP60编码基因。测定了HSP60编码区的DNA序列，并根据DNA序列预测了编码蛋白的氨基酸序列。将合成肽(50nmol)与弗氏完全佐剂乳化后注射到大鼠体内。比较链球菌热休克蛋白60和牛视网膜热休克蛋白60的氨基酸序列，发现约200个残基，同源性为47%。实验性葡萄膜炎主要是在接种视网膜HSP60衍生肽或相当于人HSP65残基245-259的链球菌HSP60衍生肽的大鼠中诱导的。视网膜和链球菌HSP60的氨基酸组成被认为对于研究白塞病的诱发机制是重要和有用的。

The observation of recurrent oral aphtha preceding ocular inflammation in patients with Behcet's disease suggests a role of oral Streptococcus in the etiology of this disease. Heat-treated Streptoccus antigen can induce ocular inflammation or systemic symptoms in Behcet's disease patients. Furthermore, the presence of an autoantibody against retinat heat-shock protein 60 (HSP60) has been detected in the sera of these patients. Injection of extracted retinal HSP60 also induces experimental uveitis in treated rats. The characteristics of retinal HSP60 and HSP60 from Streptoccus pyogenes (S. pyogenes) were evaluated using a molecular biological approach. The gene encoding HSP60 was isolated by polymerase chain reaction from a bovine retinal cDNA library and from S. pyogenes DNA. The DNA sequence of the HSP60 coding region was determined, and the amino acid sequences of the encoded proteins were predicted from the DNA sequence. The synthetic peptide (50 nmol) was emulsified with Freund's complete adjuvant and injected into rats. Comparison of the amino acid sequences of Streptococcal and bovine retinal HSP60 revealed about 200 residue region with 47% homology. Experimental uveitis was mainly induced in rats inoculated with retinal HSP60-derived peptide or Streptococcus HSP60-derived peptide that is equivalent to residues 245-259 of human HSP65. Retinal and Streptococcal HSP60 amino acid composition are thought to be important and useful for investigating the mechanisms involved in the induction of Behcet's disease.