Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease.

Abstract

Antibodies to aminoacyl-tRNA synthetases (anti-Jo-i, anti-PL-7, anti-PL-12) have been found in the serum of some patients with polymyositis (PM). Patients with these antibodies have an unusually high rate of interstitial lung disease (ILD) in association with their PM. Two patients (K.J. and B.T.) with severe ILD and PM were found to have antibodies to a cytoplasmic antigen, but tests to determine whether the antigen was an aminoacyl-tRNA synthetase were negative, including tests of LJ serum for inhibitory effects on the 20 synthetases. KJ immunoprecipitates did not contain tRNA, in contrast to antisynthetase sera. When IgG samples were added to a reticulocyte in vitro translation system at a concentration of 0.3 mg/mi, KJ IgG inhibited globin mRNA translation by 98%, while anti-Jo-i IgG inhibited 62% and normal IgG had little effect. Thus, both anti-LJ and the antisynthetases are directed at antigens that are involved in translation and protein synthesis, and both are associated with the syndrome of lung disease and PM. This syndrome may be associated with antibodies to translation-related proteins in general, which may have implications for the link of PM and enteroviruses, which are mRNA viruses.

Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase.

“…IPs for protein and nucleic acid analyses were performed as previously described (5 (5) or immunoprecipitate ofanti-OJ sera from HeLa cell extract. The procedure for immunoblotting using whole extract was as previously described ( 19) with the following modifications. After 8-9% SDS-PAGE and transfer to nitrocellulose, strips were blocked with 5% bovine nonfat milk in Tris-saline blotting buffer.…”

“…Each aminoacyl-tRNA synthetase catalyzes an aminoacylation reaction (tRNA charging) in which its particular amino acid is covalently linked to the cognate tRNA. The ability of sera to inhibit the activity of each synthetase was tested individually as described previously (5,19 calf liver extract. The enzyme source was preincubated with patient or control serum, usually diluted 1:10.…”

“…As a result of nonspecific inhibition by some sera, and as determined by previous studies, inhibition by a serum was considered significant only if > 50% of activity was inhibited as compared with the average results with at least two normal sera. For confirmation of significant inhibition, purified IgG was obtained by DEAE chromatography as described previously (5,19).…”

Antibody to signal recognition particle in polymyositis

“…The Ro (SS-A) and La (SS-B) RNAs were precipitated by serum 11, and weakly precipitated by serum 9, while the Ro (SS-A) RNAs, but not the La (SS-B) RNAs, were weakly precipitated by serum 2 (Figure 1). All the anti-SRP-positive sera were tested for the presence of antibodies to Jo-1 and to KJ antigens by ELISA (21,38), and all sera were negative. In all described patients, sera containing antisynthetases immunoprecipitated the respective tRNA.…”

Cloning of a complementary DNA coding for the 100-kD antigenic protein of the PM-Scl autoantigen.

“…Immunoprecipitation of35S-labeled HeLa cell extracts with anti-PM-Scl shows a group of 1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] proteins that appear to be a complex (8,9). A prominent band is seen at 100 kD, but bands are present from 20 to 110 kD.…”