Anti-KS: Identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease

Autoantibodies to five of the aminoacyl-transfer RNA (tRNA) synthetases hav e been described, and each is associated with a syndrome of inflammatory my opathy 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 d escribed anti-synthetase or other reported tRNA-related Abs, along with a p rotein of 65 kDa. KS serum and IgG fraction each showed significant (88%) i nhibition of asparaginyl-tRNA synthetase (AsnRS) activity, but not of any o f the other 19 aminoacyl-tRNA synthetase activities, Among 884 patients wit h connective tissue diseases tested, only two other sera were found to immu noprecipitate tRNAs and proteins of identical gel mobility. These two and K S showed identical immunodiffusion lines using HeLa cell extract. The new s era significantly inhibited AsnRS without significant effects on other synt hetases tested. Both patients had ILD but neither had evidence of myositis, These data strongly suggest that these three sera have autoantibodies to A snRS, representing a sixth anti-synthetase. Anti-KS was more closely associ ated with ILD than with myositis, Further study of this Abs might prove use ful in dissecting the stimuli responsible for the genesis of anti-synthetas e autoantibodies.