Background/Purpose: Histidyl-transfer RNA synthetase (HisRS, Jo-1) is a major autoantigen in myositis with lung involvement^1-4. Simultaneous presence of anti-Jo-1 and anti-Ro52 antibodies has been demonstrated in patients with myositis^5-7. We investigated the presence of HisRS in the extracellular compartments plasma, sera and bronchoalveolar lavage fluid (BALF). In addition, the occurrence of anti-Jo-1 antibody isotypes as well as anti-nuclear antibodies (ANA) was evaluated in BALF and sera from patients with myositis.

Methods: HisRS was measured in sera, plasma and BALF from patients with myositis (in both anti-Jo-1 positive and anti-Jo-1 negative patients), sarcoidosis, rheumatoid arthritis (RA) and healthy controls (HC) by dot-blot, western-blot, immunoprecipitation and mass spectrometry. The presence in BALF and sera of anti-Jo-1 isotypes and ANA was analysed by ELISA and addressable laser bead immunoassay.

Results: HisRS was detected in sera, plasma and BALF of patients with myositis, sarcoidosis and RA, and in HC. Systemic HisRS levels were significantly elevated in anti-Jo-1 positive myositis (14 out of 20 sera) compared to anti-Jo-1 negative myositis (10/18), sarcoidosis (0/8) and RA (3/15) patients, and HC (5/23). In BALF, significant levels of HisRS were detected in 6/8 HC and 5/8 sarcoidosis, compared to 4/8 myositis (2 anti-Jo-1 positive and 2 anti-Jo-1 negative). Our results suggest the presence of a factor in BALF with high binding capacity for HisRS and HisRS complexed with anti-HisRS-N-terminal antibody. C1q-immune complexes (IC) binding HisRS were not the binding factor. However, anti-Jo-1 antibodies as well as anti-Ro52 IgG were identified in myositis BALF (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). Furthermore, a positive correlation between the presence of anti-Jo-1 IgG and anti-Ro52 IgG in myositis BALF was identified (r²=0.881; p=0.007).

Conclusion: HisRS was detected both in blood and BALF. The identification of extracellular HisRS, anti-Jo-1 isotypes and anti-Ro52 IgG in myositis BALF may provide additional clues for the development of autoimmunity in the lungs. ¹Bernstein RM et al Br Med J (Clin Res Ed). 1984 Jul 21;289(6438):151-2; ²Marguerie C et al Q J Med. 1990 Oct;77(282):1019-38; ³Hervier B et al Eur Respir J. 2013 Nov;42(5):1271-82; ⁴Hamaguchi Y et al PLoS One. 2013;8(4):e60442; ⁵La Corte R et al Autoimmunity 2006 May;39(3):249-53; ⁶Brouwer R et al Ann Rheum Dis. 2001 Feb;60(2):116-23; ⁷Rutjes SA et al Clin Exp Immunol. 1997 Jul;109(1):32-40.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/extracellular-histidyl-trna-synthetase-in-myositis/