Immunosuppressive therapy for myasthenia gravis.

Research Project

Project/Area Number	10671253
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Thoracic surgery
Research Institution	Osaka University
Principal Investigator	OKUMURA Meinoshin Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40252647)
Co-Investigator(Kenkyū-buntansha)	MINAMI Masato Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10240847) YOON Hyung-eun Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (50283768) MIYOSHI Shinichiro Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助教授 (00190827) TAKEDA Shin-ichi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30236468)
Project Period (FY)	1998 – 1999
Project Status	Completed (Fiscal Year 1999)
Budget Amount *help	¥3,700,000 (Direct Cost: ¥3,700,000) Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000) Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywords	Myasthenia gravis / Immunosuppressive therapy / アセチルコリンレセプター / T細胞
Research Abstract	Myasthenia gravis is an autoimmune disease characterized by weakness of striated muscles caused by the autoantibodies against nicotinic acetylcholine receptors at neuro-muscular junctions. Although extended thymectomy is established as the effective treatment for this disease, thymectomy fails in some cases where steroid therapy or plasma exchange become mandatory. Recently, immuno-suppressive reagents represented by azathiopurin has been administrated for thymectomy-resistant myasthenic patients. We have tried cyclosporine A-based immunosuppressive therapy for thymectomy-resistant myasthenia gravis patients these several years, and reported the successful long-term results of this treatment at 52nd Annual Meeting of the Japanese Association for Thoracic and Cardiovascular Sugery in Sendai on November 1999. Long-term non-specific immunosuppressive therapy, however, retains a risk of opportunistic infection, and therefore, development of an immunosuppressive therapy directed specifically to the T or B lymphocytes responding to autoantigens is required. Because autoantibody production is dependent on T cells in myasthenia gravis, an approach to suppress T cells recognizing acetylcholine receptor was adopted. In the first place, we attempted to establish the T cell clone specific to acetylcholine receptor by using 35 synthesized peptides composed of approximately 20 amino acids covering the full sequence of alpha subunit of nicotinic acetylcholine receptor as antigens. Lymphocytes obtained from the thymuses of 2 myasthenic patients prepared was subjected to the study. Acetylcholine receptor-specific T cell clone was established in 1 patient. This clone was found to recognize one of the peptide pool (NLKWNPDDYGGVKKIHIPSEK). An attempt to determine the aminoacid residue to induce anergy in this T cell clone is currently undertaken.