多発性筋炎・皮膚筋炎における自己抗体とその臨床免疫学的意義 [in Japanese] Autoantibodies and their clinical significance in idiopathic inflammatory myopathies ; polymyositis/dermatomyositis and related conditions [in Japanese]
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多発性筋炎/皮膚筋炎（polymyositis/dermatomyositis : PM/DM）は，筋力低下を主徴とする慢性炎症性疾患で，その臨床像は多彩である．本疾患においても他の膠原病と同様，種々の細胞成分に対する自己抗体が高率に検出される．特に，PM/DMに特異的に見出される自己抗体（myositis-specific autoantibodies ; MSAs）は，診断，病型の分類，予後の推定，治療法の決定など臨床的に有用である．さらに，かかる自己抗体が標的とする自己抗原が細胞内の重要な生物学的機能を持つ酵素や調節因子であることが同定され，自己抗体産生機序を考える上で重要な情報をもたらしている．とくに，PMに特異的な抗アミノアシルtRNA合成酵素抗体や抗SRP抗体などが蛋白合成・翻訳と関連する細胞質蛋白を標的するのに対し，DMに特異的な抗Mi-2抗体や抗体p155抗体などが核内転写調節因子を標的とすることは，自己抗体と病態形成との関連を考える上で注目される．さらに，従来，自己抗体が稀とされてきた，amyopathic DMの抗CADM-140抗体や悪性腫瘍関連筋炎の抗p155抗体は早期診断・治療など臨床的に有用なばかりでなく，これらの疾患の病因追究に大きな手掛かりを与えるものと期待される．本稿ではPM/DMにおける自己抗体とその対応抗原や臨床的意義について，最近の知見を含め概説する．<br>
The inflammatory muscle diseases, polymyositis (PM) and dermatomyositis (DM) are systemic connective tissue disorders characterized by chronic inflammation in skeletal muscle and involvement of various systemic organs. The pathogenesis of these heterogeneous diseases is unknown, but appear to mediate an autoimmune disorder that culminates in the tissue damage. Autoantibodies directed against various cellular constituents have been detected in patients with PM/DM, and 40-50% of patients have autoantibodies (myositis-specific antibodies : MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with characteristic clinical features and therefore provide us useful information for diagnosis, patient classification as well as predict of signs, symptoms of myositis, response to treatment, and prognosis.<br> Autoantibodies to the cytoplasmic antigens, that are involved in protein synthesis or translation related proteins, are seen in patients with PM. Autoantibodies to eight of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "anti-synthetase syndrome." However, certain differences of the clinical features associated with each anti-synthetase have been noted, although their similarity is impressive. Anti-signal recognition particle antibodies are associated with severe, refractory myositis that differs significantly from anti-synthetase syndrome. Autoantibodies to the nuclear antigen, Mi-2 that is a transcription-regulating protein, are specifically seen in patients with DM responsive to corticosteroid therapy.<br> In recent years, novel MSAs have been identified in clinically amyopathic dermatomyositis (anti-CADM-140 antibodies) and malignancy-associated myositis (anti-p155 and p155/p140 antibodies), in which autoantibodies have been thought to be negative. For understanding the pathogenic mechanisms of PM/DM, it is important to elucidate the relationship between these novel MSAs and their related clinical entities.<br> Recently the nature of the target MSA autoantigens has been characterized using molecular biology and proteomic techniques. However, the mechanism of development of MSAs remains unknown. Further analysis of the molecular structure and biological function of target autoantigens recognized by these MSAs might provide the clues to the understanding of the etiology and pathogenesis of these disorders.<br>
- Jpn. J. Clin. Immunol.
Jpn. J. Clin. Immunol. 30(6), 444-454, 2007-12-31
The Japan Society for Clinical Immunology