Session Information
Date: Saturday, November 6, 2021
Session Title: B Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster (0001–0010)
Session Type: Poster Session A
Session Time: 8:30AM-10:30AM
Background/Purpose: Autoantibodies are thought to play a key role in the pathogenesis of idiopathic inflammatory myopathies (IIM). However, 40% of IIM patients, even those with clinical manifestations of anti-synthetase syndrome (ASS), test seronegative to all known myositis specific autoantibodies (MSAs). Therefore, we hypothesized the existence of new potential autoantigens and we included all human cytoplasmic aminoacyl tRNA synthetases (aaRS) in an autoantibody screening of patients with IIM.
Methods: Plasma samples and clinical data from 217 IIM patients were collected from the Karolinska University Hospital myositis cohort. Fulfillment of the 2017 classification criteria (1) for IIM and Connor’s criteria (2) for ASS was verified for all patients. Patients were divided into two groups based on the ASS status (not available for 2/217 patients) and clinical manifestations were compared. Autoantibodies (MSAs and myositis associated autoantibodies (MAAs)) were tested in the clinic by standardized immunoassays (ELISA, line lot or immunoprecipitation). The 217 plasma samples were screened, using a multiplex bead array assay, for the presence of autoantibodies against a panel of 118 recombinant protein variants, representing 33 myositis-related proteins, including all 20 cytoplasmic aaRS.
Results: Fifty patients with and 165 without ASS were identified. In the non-ASS group, 69% were seronegative for MSAs. Frequency of muscle and skin involvement did not statistically differ between the two groups, while Raynaud’s phenomenon, arthritis, ILD and cardiac disease were statistically more frequent in the ASS group. On the contrary, dysphagia was statistically more prevalent among the non-ASS patients. By performing the multiplex assay, we could confirm reactivity to Jo1, PL-12, PL-7, and EJ in 44/49 patients with ASS, but not to OJ (1 patient) in the ASS group. We identified patients positive for anti-Zo (n=5), -KS (n=2) and -HA (n=3), 9/10 from the non-ASS group. In addition, we identified 12 patients positive for autoantibodies targeting other aaRS (3 from the ASS group, and 9 from the non-ASS group). These novel reactivities could be confirmed by ELISA. Ten of 22 reactivities were identified in patients previously known as seronegative.
Conclusion: Our results suggest that all aaRS may become autoantigenic. Autoantibodies against new aaRS might be found in plasma of patients previously classified as seronegative with potential high clinical relevance.
References
1. Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups. Arthritis & Rheumatology. 2017;69(12):2271-82.
2. Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial Lung Disease Associated With the Idiopathic Inflammatory Myopathies: What Progress Has Been Made in the Past 35 Years? Chest. 2010;138(6):1464-74.
To cite this abstract in AMA style:
Preger C, Notarnicola A, Hellström C, Wigren E, Cerqueira C, Nilsson P, Lundberg I, Persson H, Gräslund S, Jakobsson P. Autoantigenic Properties Indicated for the Entire Aminoacyl tRNA Synthetase Family in Idiopathic Inflammatory Myopathies [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/autoantigenic-properties-indicated-for-the-entire-aminoacyl-trna-synthetase-family-in-idiopathic-inflammatory-myopathies/. Accessed February 2, 2023.« Back to ACR Convergence 2021
ACR Meeting Abstracts - https://acrabstracts.org/abstract/autoantigenic-properties-indicated-for-the-entire-aminoacyl-trna-synthetase-family-in-idiopathic-inflammatory-myopathies/