THU0065 Clinical significance of anti-asparaginyl trna synthetase autoantibodies. (1st June 2001)

• Record Type: Journal Article
• Authors: Hirakata, M; Suwa, A; Nojima, T; Suzuki, M; Nagai, S; Mimori, T; Targoff, IN
• Is Part Of: Annals of the rheumatic diseases. Volume 60(2001)Supplement 1
• Page Start: A359
• Page End: A359
• Publication Date: 2001-06-01
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2001.909
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Autoantibodies to 5 of the aminoacyl tRNA synthetases (those for histidine, threonine, alanine, isoleucine and glycine) have been described, and each is associated with a similar syndrome of myositis (PM or DM) with interstitial lung disease (ILD), arthritis, and other features. 1 We have identified novel autoantibodies to asparaginyl tRNA synthetase (AsnRS), 2 but the clinical significance of this sixth anti-synthetase antibody has not been well-defined. Objectives: The aim of the present study was to identify patients with anti-AsnRS and elucidate the clinical and immunogenetic features of this sixth anti-synthetase autoantibodies. Methods: Sera from more than 2, 500 patients with connective tissue disease including myositis and ILD in collaborating centres, and control sera were examined for anti-AsnRS antibodies by immunoprecipitation. Positive sera and controls were tested for the ability to inhibit AsnRS by preincubation of the enzyme source with the serum. The HLA-class II (DRB1, DQA1, DQB1, DPB1) alleles were identified from RFLP of PCR-amplified genomic DNA. The concentration of KL-6 (a new marker for ILD) in serum was determined by a specific ELISA. 3 Results: Anti-KS antibodies were identified in the sera of 8 patients (5 Japanese, 1 U. S., 1 German, 1 Korean), by immunoprecipitation of the same distinctive set of tRNAs and protein that differed from those precipitated by the other 5 anti-synthetases, and showed specific inhibition of AsnRS activity. Two of these patients had DM, but seven of 8 (88%) had ILD. Four (50%) had arthritis, and one had Raynaud 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. Furthermore, four of 5 patients in whom KL-6 levels were measured, showed markedly elevated levels (mean level 919.8 U/ml; normal < 500 U/ml). Interestingly, all four Japanese patients tested had DR 2 (DRB1*1501/1502), compared to 33% of healthy controls. Conclusion: 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. References: Targoff IN. Rheum Dis Clin North Am. 1994;20:857–80 Hirakata M, et al . J Immunol. 1999;162:2315–20 Nakajima H, et al . J Rheumatol. 2000;27:1164–70