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.
Bernstein RM., et al. Br Med J (Clin Res Ed). 1984 Jul 21;289(6438):151–2;
Marguerie C., et al. Q J Med. 1990 Oct;77(282):1019–38;
Hervier B., et al. Eur Respir J. 2013 Nov;42(5):1271–82;
Hamaguchi Y., et al. PLoS One. 2013;8(4):e60442;
La Corte R., et al. Autoimmunity. 2006 May;39(3):249–53;
Brouwer R., et al. Ann Rheum Dis. 2001 Feb;60(2):116–23;
Rutjes SA., et al. Clin Exp Immunol. 1997 Jul;109(1):32–40.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.