Kuwana M, Kaburaki J, Mimori T, Tojo T, Homma M
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Arthritis Rheum. 1993 Oct;36(10):1406-13. doi: 10.1002/art.1780361013.
To elucidate the clinical and immunogenetic associations with reactivity to autoantigenic epitopes on DNA topoisomerase I (topo I) recognized by sera from patients with systemic sclerosis (SSc).
Autoantigenic epitopes on topo I were identified by screening an epitope library constructed from topo I complementary DNA restriction fragments using autoimmune anti-topo I-positive sera as a probe. Epitope reactivities of sera from 43 anti-topo I-positive SSc patients were surveyed by immunoblotting, and associations with clinical symptoms and HLA-DR types were examined.
Four different epitope regions were identified on the topo I molecule. Immunoreactivity to the region encompassing amino acid residues 658-700, termed ER4, was found to be associated with diffuse cutaneous SSc, progressive pulmonary interstitial fibrosis, and poor prognosis for 15-year survival. SSc patients with ER4 reactivity frequently displayed the DR2/DRw52 phenotype.
Molecular analysis of precise antigenic epitopes on topo I is helpful in classifying clinical subsets of SSc.
阐明系统性硬化症（SSc）患者血清所识别的DNA拓扑异构酶I（拓扑异构酶I）自身抗原表位的反应性与临床及免疫遗传学之间的关联。
以自身免疫性抗拓扑异构酶I阳性血清为探针，通过筛选由拓扑异构酶I互补DNA限制性片段构建的表位文库，确定拓扑异构酶I上的自身抗原表位。采用免疫印迹法检测43例抗拓扑异构酶I阳性SSc患者血清的表位反应性，并检查其与临床症状和HLA-DR类型的关联。
在拓扑异构酶I分子上鉴定出四个不同的表位区域。发现对包含氨基酸残基658 - 700的区域（称为ER4）的免疫反应性与弥漫性皮肤型SSc、进行性肺间质纤维化以及15年生存率低相关。具有ER4反应性的SSc患者常表现出DR2/DRw52表型。
对拓扑异构酶I上精确抗原表位的分子分析有助于对SSc的临床亚组进行分类。
