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Abstract
Background
Autoimmune myositis (rheumatic muscle inflammation) associated with interstitial lung disease (ILD) and arthritis is strongly correlated with the presence of anti-histidyl tRNA synthetase (HisRS) autoantibodies.1
Objectives
The aims of this study were to investigate: 1) myositis IgG reactivity against HisRS conformational epitopes; and 2) association between clinical manifestations and anti-HisRS reactivity profiles.
Methods
Serum IgG was isolated using a protein G affinity column (from 25 anti-HisRS negative (-) and 19 anti-HisRS positive (+) myositis sera and 24 age/gender matched healthy controls, HC). Autoantibody reactivity was tested by in house ELISA developed against HisRS full-length protein and three HisRS conformational epitopes (WHEP domain - localised in the N-terminal; HisRS without WHEP (HisRS_WHEP); and ABD - anticodon-binding domain located in the C-terminal). Correlations between diagnosis, clinical manifestations and anti-HisRS IgG reactivity were evaluated.
Results
HisRS(+) myositis IgG displayed stronger reactivity against full-length HisRS and HisRS_WHEP (median 372 ng/mL and 334 ng/mL, respectively), compared to WHEP and ABD (6.38 and 6.48 ng/mL). The strongest anti-full-length HisRS reactivity (>371 ng/mL) was detected in patients presenting ILD (10/10 of patients), arthritis (6/10) and polymyositis diagnosis (PM 9/10), in comparison to patients with low anti-HisRS reactivity (<23 ng/mL, ILD - 5/6; arthritis - 3/6; PM - 5/6) or no anti-HisRS reactivity (ILD - 10/28; Arthritis - 8/28; PM - 15/28). On the contrary, myositis patients displaying no anti-HisRS reactivity were largely diagnosed with DM (11/28), skin rash (11/28) and dysphagia (6/28) when compared to patients with the highest anti-full-length HisRS reactivity (1 out of 10 patients was diagnosed with DM, skin rash or dysphagia). Similar associations were observed between the degree of anti-HisRS_WHEP, anti-WHEP or anti-ABD reactivities and manifestations of ILD, arthritis, skin rash or dysphagia, and DM or PM diagnosis. No anti-HisRS reactivity was detected in the HC group.
Conclusions
This study provides evidences for a possible underlying role of anti-HisRS autoantibodies in the pathogenesis of myositis with interstitial lung disease and joint involvement.
Reference
[1] Hamaguchi Y, Fujimoto M, Matsushita T, et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS One2013;8(4):e60442.
Disclosure of Interest
None declared