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SAT0189 Characterization of Extracellular Histidyl-TRNA Synthetase in Myositis
  1. C. Fernandes Cerqueira1,
  2. A. Sohrabian2,
  3. I. Albrecht1,
  4. A. Notarnicola1,
  5. E. Ossipova1,
  6. J. Lengqvist1,
  7. M. Fati3,
  8. G.J. Pruijn4,
  9. J. Grunewald3,
  10. J. Rönnelid2,
  11. I.E. Lundberg1,
  12. P.-J. Jakobsson1
  1. 1Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm
  2. 2Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala
  3. 3Respiratory Medicine Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  4. 4Department of Biomolecular Chemistry, Radboud Institute for Molecular Life Sciences and Institute for Molecules and Materials, Radboud University, Nijmegen, Netherlands

Abstract

Background Histidyl-transfer RNA synthetase (HisRS) is a major autoantigen in myositis with lung involvement1–4. Simultaneous presence of anti-HisRS and anti-Ro52 antibodies has been demonstrated in patients with myositis5–7.

Objectives We investigated the presence of HisRS in the extracellular compartments plasma, sera and bronchoalveolar lavage fluid (BAL). In addition, the occurrence of anti-HisRS antibody isotypes as well as other auto-reactivities was evaluated in BAL and sera from patients with myositis.

Methods HisRS was measured in sera, plasma and BAL from myositis (anti-HisRS antibody positive, anti-Jo1+ and negative, anti-Jo1-), sarcoidosis, rheumatoid arthritis (RA) patients and healthy controls (HC) by dot-blot, western-blot, immunoprecipitation and mass spectrometry. The presence in BAL and sera of anti-Jo1 isotypes and other ANA-associated autoantibodies was analysed by ELISA and addressable laser bead immunoassay.

Results HisRS was detected in sera, plasma and BAL of patients with myositis, sarcoidosis and RA and in HC. HisRS systemic levels were elevated in anti-Jo1+ myositis (14 out of 20 sera) compared to anti-Jo1- myositis (10/18), sarcoidosis (0/8) and RA (3/15) patients, and HC (5/23). In BAL, significant levels of HisRS were detected in 6/8 HC and 5/8 sarcoidosis, compared to 4/8 myositis (2 anti-Jo1+ and 2 anti-Jo1-). Our results demonstrated the presence of a factor in BAL with high binding capacity for HisRS and HisRS complexed with anti-HisRS-N-terminal antibody. C1q-binding immune complexes (IC) containing HisRS were not the binding factor. However, anti-Jo1 isotypes as well as anti-Ro52 IgG were identified in both BAL (5/8 patients were positive for anti-Jo1 IgG, 3/8 for anti-Jo1 IgA, 3/8 for anti-Jo1 IgM and 4/8 for anti-Ro52 IgG) and sera (5/8 for anti-Jo1 IgG, 3/8 for anti-Jo1 IgA, 4/8 for anti-Jo1 IgM and 3/8 for anti-Ro52 IgG) from patients with myositis. Furthermore, a positive correlation between the presence of anti-Jo1 IgG and anti-Ro52 IgG in BAL was identified (r2=0,881; p=0,007).

Conclusions HisRS was detected both in blood and BAL fluid. The identification of extracellular HisRS, anti-Jo1 isotypes and anti-Ro52 in myositis BAL may provide additional clues for the development of autoimmunity in the lungs.

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Disclosure of Interest None declared

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