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アミノアシルtRNA合成酵素に対する自己抗体の分子免疫学的性状に関する研究

氨酰-tRNA合成酶自身抗体的分子免疫学特性研究

基本信息

批准号：
09770326
负责人：
中村邦夫
金额：
$ 1.22万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Encouragement of Young Scientists (A)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

【目的】抗アミノアシルtRNA合成酵素(ARS)抗体の臨床・免疫遺伝学的特徴の追究を目的とした。【方法】(1)教室で自己抗体を検索した1082例(多発性筋炎118;SLE380;強皮症180;慢性関節リウマチ56;重複症候群94;特発性間質性肺炎109;関節痛,皮疹を有する症例145例)を対象とした。(2)抗ARS抗体の検索:患者血清中の自己抗体検索にはLemer-steitzに準じ,免疫沈降法で調べた。そのため,核酸成分の分析には^<32>P-燐酸標識HeLa細胞抽出物,蛋白成分の分析には^<35>S-メチオニン標識HeLa細胞抽出物を用いた。(3)HLAクラスII遺伝子は,同抗体陽性例および患者,健常人コントロール末梢血白血球より抽出したgenomicDNAをDRB1,DQA1,DQB1,DPB1各々に特異的なブライマーを用いてPCR増幅する。次に,増幅DNAを種々の制限酵素で切断し,その産物の大きさを比較検討(PCR-RFLP法)し,対立遺伝子を決定した。【結果】(1)抗HisRS 22;抗GlyRS 12:抗AlaRS 7;抗ThrRS 5;抗IIeRS 3例を見い出した。(2)筋炎は抗His-,抗Thr-,抗lle-R抗体陽性全例に認めたが,抗GlyRS(50%),抗AlaRS(14%)と低頻度であった。一方,抗HisRSの2例以外,間質性肺炎を全例に認めた。(3)抗HisRS抗体陽性例はDRBl^*0405-DQAl^*0302-DQB1^*401を80%,抗AlaRS抗体陽性例はDRBl^*501-DQAl^*0102-DQBl^*0602を57%と高頻度に持っていた。【結語】抗ARS抗体は間質性肺炎,筋炎,多関節炎と関連するが,各々の特異性で関連症状が異なっていた。その一因としてHLAクラスII遺伝子(免疫遺伝学的背景)の相違が考えられた。

[Objective] The purpose of this study is to investigate the clinical and immunogenetic characteristics of anti-Amiasil tRNA synthetase (ARS) antibodies. [Methods](1) In the classroom, 1082 cases of autoantibodies were detected (118 cases of polymyositis; 380 cases of SLE; 180 cases of scleroderma; 56 cases of chronic arthritis; 94 cases of duplication syndrome; 109 cases of idiopathic interstitial pneumonia; 145 cases of arthralgia and rash). (2)Anti-ARS antibody detection: The detection of anti-ARS antibodies in patient serum is based on Lemer-steitz method, and immunosedimentation method is used to adjust the detection. The analysis of nucleic acid <32>composition and protein composition of HeLa cell <35>extracts was carried out. (3)HLA virus II gene was amplified by PCR in antibody-positive cases, patients and healthy individuals. Secondly, the restriction enzymes of amplified DNA were cut off, and the products were compared by PCR-RFLP method to determine the identity of the genes. [Results](1) Anti-HisRS 22, anti-GlyRS 12, anti-AlaRS 7, anti-ThrRS 5, anti-IIeRS 3 cases were detected. (2)Anti-His-, anti-Thr-, anti-lle-R antibodies were detected in all cases, anti-GlyRS (50%), anti-AlaRS (14%) and low frequency. All cases of interstitial pneumonia were recognized except 2 cases of anti-HisRS. (3)Anti-HisRS antibody positive cases were DRB1 ^*0405-DQAl^*0302-DQB1^*401 in 80% and anti-AlaRS antibody positive cases were DRB1 ^*501-DQAl^*0102-DQB1 ^*0602 in 57% with high frequency. [Conclusion] Anti-ARS antibodies are associated with interstitial pneumonia, tendonitis, and polyarthritis, and each has specific associated symptoms. A study of HLA II genes (background in immunology)