Immunological characterization of heterochromatin protein p25脽 autoantibodies and relationship with centromere autoantibodies and pulmonary fibrosis in systemic scleroderma
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- 作者：Kiyoshi Furuta ; Bernhard Hildebrandt ; Sayako Matsuoka ; Kendo Kiyosawa ; Georg Reimer ; Christoph Luderschmidt ; Edward K. L. Chan and E. M. Tan
- 关键词：Key words ; Autoantibody ; Heterochromatin protein ; Systemic scleroderma ; Anticentromere antibody
- 刊名：Journal of Molecular Medicine
- 出版时间：December 1997
- 出版年：1997
- 期刊代码：148_0946-2716
- 类别：bio
- 卷：76
- 期：1
- 页码：54-60
- 数据来源：sp
摘要
Anticentromere antibodies (ACA) are immunological markers for the subset of systemic scleroderma with the symptoms calcinosis cutis, Raynaud’s phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (CREST). In western blotting, some ACA-positive sera also recognize a doublet of 23 kDa (p23) and 25 kDa (p25) in addition to centromere protein antigens A (17 kDa), B (80 kDa), and C (140 kDa). Two forms of p25 have been shown to be human homologues of Drosophila heterochromatin-associated protein HP1. One form of p25 (p25β) which was recently cloned in this laboratory was used to evaluate anti-p25β antibody response in scleroderma sera. Of 318 scleroderma sera 42 had ACA (13.2%), and 16 of the 42 sera (38%) had anti-p25β antibodies. On the other hand, 5 of 276 ACA-negative sera (1.8%) showed anti-p25β antibody response, demonstrating that anti-p25β antibody is significantly associated with the ACA response (P<10–8). Clinically the anti-p25β response was significantly associated with the CREST syndrome. Fourteen (36.8%) of 38 CREST patients compared to seven (2.5%) of 280 patients with other forms of scleroderma were anti-p25β antibody positive (P<10–8). The 14 CREST patients with anti-p25β antibodies had significantly more interstitial lung disease than those without anti-p25β antibodies (P<0.003). There was also a tendency to increased liver involvement. Two dominant autoepitopes in p25β were determined by western blotting using p25β recombinant fragments. In immunofluorescence C-terminal specific antibodies showed staining of heterochromatin, but N-terminal specific antibodies showed no staining. Interestingly, the majority of sera reacted preferentially with one or the other of the two dominant autoepitopes.