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.
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