Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis

J Biol Chem. 2014 Jul 11;289(28):19269-75. doi: 10.1074/jbc.C114.571026. Epub 2014 Jun 4.


Inflammatory and debilitating myositis and interstitial lung disease are commonly associated with autoantibodies (anti-Jo-1 antibodies) to cytoplasmic histidyl-tRNA synthetase (HisRS). Anti-Jo-1 antibodies from different disease-afflicted patients react mostly with spatially separated epitopes in the three-dimensional structure of human HisRS. We noted that two HisRS splice variants (SVs) include these spatially separated regions, but each SV lacks the HisRS catalytic domain. Despite the large deletions, the two SVs cross-react with a substantial population of anti-Jo-l antibodies from myositis patients. Moreover, expression of at least one of the SVs is up-regulated in dermatomyositis patients, and cell-based experiments show that both SVs and HisRS can be secreted. We suggest that, in patients with inflammatory myositis, anti-Jo-1 antibodies may have extracellular activity.

Keywords: Aminoacyl-tRNA Synthetase; Anti-Jo-1 Autoantibody; Autoimmune Disease; Dermatomyositis; Epitope Mapping; Immunology; Myositis; Secretion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Autoantibodies / immunology
  • Autoantibodies / metabolism*
  • Cell Line, Tumor
  • Epitopes / genetics
  • Epitopes / immunology
  • Epitopes / metabolism*
  • Histidine-tRNA Ligase / genetics
  • Histidine-tRNA Ligase / immunology
  • Histidine-tRNA Ligase / metabolism*
  • Humans
  • Inflammation / enzymology
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Myositis / enzymology*
  • Myositis / genetics
  • Myositis / immunology
  • Myositis / pathology
  • Protein Structure, Tertiary


  • Autoantibodies
  • Epitopes
  • Histidine-tRNA Ligase