2007 Fiscal Year Final Research Report Summary
Autoimmune Mechanism of Inflammatory Muscle Disease by Myositis-specific Autnantibodies
| Project/Area Number |
17591055
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Keio University |
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Principal Investigator |
HIRAKATA Michito Keio University, School of Medicine, Assistant Professor (30199046)
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| Project Period (FY) |
2005 – 2007
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| Keywords | polymyositis / dermatomyositis / autoantibodies / autoantigen / aminoacyl tRNA synthetase / aignal recognition particle / autoimmunity / immunogenetics / HLA class II |
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| Research Abstract |
[Clinical and immunological features in Japanese patients with anti-PMS1 autoantibodies] In the in vitro transcriptioin/translation immunoprecipitation assay, eleven sera that immunoprecipitated the 120 kDa polypeptide corresponding to the PMS 1 antigen, were identified. Among these 11 patients, 6 had the PM-overlap syndrome, 2 had DM, 2 had ILD, and 1 had SSc. Eight of 11 (73%) had myositis, while 6 (55%) had ILD and arthritis. In standard immunoprecipitation studies, patients with anti-PMS1 were noted to have other autoantibodies including anti-aminoacyl tRNA synthetases (anti-Jo-1: 1 patient, anti-EJ: 1 patient, anti-PL-7: 1 patient), anti-U1 RNP (3 patients), anti-Sm (2 patients), and anti-DNA topoisomerase I (1 patient) antibodies. It should be noted that these sera did not recognize other proteins involved in DNA repairand remodeling, as reported in North American patients. These results indicate that anti-PMS1 autoantibodies are associated with myositis-overlap syndrome and may
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assist in identification of patients at increased risk of ILD and arthritis.
[Genotypic features of Japanese patients with myositis-specific autoantibodies] To explore the possibility that restrictions on antigen presentation are a key factor, we determined the immunogenetic phenotype of 44 Japanese patients who had the autoantibodies in conjunction with inflammatory myopathy. (1) Ten of 14 patients (71%) with anti-HisRS (8 individuals) or and-ThrRS (2 individuals) had the DRB1*0405-DQA1*0303-DQB1*0401 haplotype, compared to 22% of the controls (odds ratio (OR)= 9, P=0.001) and 13 of these 14 individuals (93%) had DR4. (2) Five of 8 patients (63%) with anti-AlaRS had DRB1*1501-DQA1*0102-DQB1*0602, compared to 9% of healthy controls (OR=17.5, P=0.002). (3) Seven of 8 patients (88%) with anti-AsnRS had DR 2 (DRB1*1501/1502), compared to 33% of healthy controls. (4) Nine of 20 patients (45%) with anti-SRP had DR 8 (DRB1*0802/08032), compared to 20% of healthy controls. Our present results indicate that anti-HisRS and anti-ThrRS antibodies have an immunogenetic association that is distinctly different from that of anti-AlaRS and anti-AsnRS autoantibodies.
[Heterogeneity of Autoimmune Responses to the Signal Recognition Particle (SRP)] To investigate the mechanisms responsible for anti-SRP induction, we studied 36 Japanese patients with anti-SRP identified among approximately 15,000 patients with connective tissue diseases using immunoprecipitation (IPP) assays using conditions that dissociate the SRP into individual polypeptide and RNA components. Ten different patterns of binding to the individual polypeptides and the 7SL-RNA could be distinguished. Sera from 9 patients (25%) directly immunoprecipitated the naked 7SL-RNA; all of them had myositis without cutaneous features of DM or malignant disease. Twenty-four patients had antibodies to the 54 kDa polypeptide (the primary target for anti-SRP antibodies in North American patients); they had lower frequencies of arthritis, compared to the 12 lacked antibodies to this polypeptide (4% vs. 36%; P<0.05). These results indicate that the SRP must trigger B cells in patients with inflammatory muscle disease when autoantibodies to this particle are produced. Less
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[Journal Article] Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase2007
Author(s)
Hirakata, M., Suwa, A., Takada, T., Sato, S., Nagai, S., Genth, E., Song, Y. W., Mimori, T., and Targoff, I. N
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Journal Title
Arthritis Rheum 56(4)
Pages: 1295-1303
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis2005
Author(s)
Sato, S., Hirakata, M., Kuwana, M., Suwa, A., Inada, S., Mimori, T., Nishikawa, T., Oddis, C. V., Ikeda, Y
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Journal Title
Arthritis Rheum 52(5)
Pages: 1571-1576
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Clinical features of Japanese patients with anti-asparaginyl tRNA synthetase autoantibodies. The Immunogenetic backgrounds2007
Author(s)
Hirakata, M., Suwa, A., Takada, T., Kaneko, Y., Sato, S., Kuwana, M
Organizer
71th Annual Meeting of American College of Rheumatology
Place of Presentation
Boston
Year and Date
2007-11-10
Description
「研究成果報告書概要(欧文)」より
