Clinical and immunogenetic features of patients with autoantibodies to asparaginyl-transfer RNA synthetase.
OBJECTIVE
We have previously described anti-KS autoantibodies and provided evidence that they are directed against asparaginyl-transfer RNA (tRNA) synthetase (AsnRS). The aim of the present study was to identify patients with anti-AsnRS autoantibodies and elucidate the clinical significance of this sixth antisynthetase antibody. In particular, we studied whether it was associated with the syndrome of myositis (polymyositis or dermatomyositis [DM]), interstitial lung disease (ILD), arthritis, and other features that had been previously associated with the 5 other anti-aminoacyl-tRNA synthetase autoantibodies.


METHODS
More than 2,500 sera from patients with connective tissue disease (including myositis and ILD) and controls were examined for anti-AsnRS autoantibodies by immunoprecipitation (IP). Positive and control sera 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 restriction fragment length polymorphism of polymerase chain reaction-amplified genomic DNA.


RESULTS
Anti-AsnRS antibodies were identified in the sera of 8 patients (5 Japanese, 1 American, 1 German, and 1 Korean) by IP of the same distinctive set of tRNA and protein that differed from those precipitated by the other 5 antisynthetases, and these antibodies showed specific inhibition of AsnRS activity. Two of these patients had DM, but 7 of 8 (88%) had ILD. Four patients (50%) had arthritis, and 1 had Raynaud's phenomenon. This antisynthetase was very rare among myositis patients (present in 0% of Japanese myositis patients), but it was found in 3% of Japanese ILD patients. Thus, most patients with anti-AsnRS had chronic ILD with or without features of connective tissue disease. Interestingly, all 4 Japanese patients tested had DR2 (DRB1*1501/1502), compared with 33% of healthy controls.


CONCLUSIONS
These results indicate that anti-AsnRS autoantibodies, like anti-alanyl-tRNA synthetase autoantibodies, have a stronger association with ILD than with myositis and may be associated with the DR2 phenotype.
Hirakata
Michito
M
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, and Seoul National University Hospital, Korea. mhirakat@sc.itc.keio.ac.jp
Suwa
Akira
A
Takada
Tetsuya
T
Sato
Shinji
S
Nagai
Sonoko
S
Genth
Ekkehard
E
Song
Yeong W
YW
Mimori
Tsuneyo
T
Targoff
Ira N
IN
D000368:Aged; D001168:Arthritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001226:Aspartate-tRNA Ligase / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D003882:Dermatomyositis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D015802:HLA-DR2 Antigen / Q000235:genetics*; D006239:Haplotypes; D006367:HeLa Cells; D006650:Histocompatibility Testing; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D017285:Polymyositis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012346:RNA, Transfer, Amino Acyl / Q000276:immunology*; D013577:Syndrome
D001323:Autoantibodies; D001324:Autoantigens; D015802:HLA-DR2 Antigen; D012346:RNA, Transfer, Amino Acyl; D001226:Aspartate-tRNA Ligase; C029194:asparaginyl-tRNA synthetase