|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 2000 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1999 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1998 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Autoantibodies to five of the aminoacyl-transfer RNA (tRNA) synthetases have been described, and each is associated with a syndrome of inflammatory myopathy with interstitial lung disease (ILD) and arthritis. Serum KS, from a patient with ILD and inflammatory arthritis without evidence of myositis, immunoprecipitated a tRNA that was distinct from that precipitated by any described anti-synthetase or other reported tRNA-related antibodies, along with a protein of 65 kDa. KS serum and IgG fraction each showed significant (88%) inhibition of asparaginyl-tRNA synthetase (AsnRS) activity, but not of any of the other 19 aminoacyl-tRNA synthetase activities.
Among 2500 patients with connective tissue diseases tested, the sera of 8 patients (5 Japanese, 1 U.S., 1 German, 1 Korean) were found to immunoprecipitate tRNAs and proteins of identical gel mobility. These sera and KS showed identical immunodiffusion lines using HeLa cell extract and significantly inhibited AsnRS without significant effects on other synthetases tested. Two of these patients had DM, but seven of 8 (88%) had ILD.Four (50%) had arthritis, and one had Raynaud's phenomenon. This anti-synthetase was very rare among myositis patients, found in <0.2% of U.S.myositis patients, and 0% of Japanese myositis patients, but was found in 3% of Japanese ILD patients. Thus, most patients with anti-AsnRS antibodies had chronic ILD with or without features of connective tissue disease. Interestingly, all four Japanese patients tested had DR 2 (DRB1^*1501/1502), compared to 33% of healthy controls.
These results indicate that anti-AsnRS antibodies, like anti-PL-12 (alanyl tRNA synthetase) antibodies, have a stronger association with ILD than with myositis, and may be associated with the DR2 phenotype.