Date: Sunday, November 13, 2016
Session Title: Muscle Biology, Myositis and Myopathies
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Idiopathic inflammatory myopathy (IIM) is an autoimmune disorder characterized by muscular as well as extra-muscular organ pathology. The anti-synthetase syndrome is specifically associated with auto-antibodies directed against amino-acyl-tRNA synthetases and encompasses a clinical spectrum comprised of myositis, interstitial lung disease, Raynauds’s phenomenon, symmetric non-erosive arthritis, mechanic’s hands, and fever. The most common autoantibody is anti-Jo-1 which targets histidyl-tRNA synthetase (HRS). Previous work assessing the reactivity of serum anti-Jo-1 antibodies with full length recombinant HRS demonstrated cross-sectional as well as longitudinal correlations with serum creatinine kinase levels, myositis visual analogue scale (VAS), arthritis VAS, and different components of the Myositis Intention to Treat Activity Index (MITAX). In the current study, we aimed to refine these correlations through more detailed assessment of the relationship between HRS epitope specificity and clinical features of the anti-synthetase syndrome.
Methods: We assessed serum reactivity (via ELISA) against overlapping sub-fragments of HRS/Jo-1 protein (Fig 1) in 139 patients with anti-Jo-1 antibodies and different patterns of organ involvement. Use of Mann U Whitney and Kruskal Wallace testing permitted statistical correlations of epitope specificity with various clinical features encompassed by the Myositis Disease Activity Assessment Tool (MDAAT).
Results: Our results indicate that defined clinical features such as joint swelling and Raynaud’s are associated with enhanced antibody binding of amino-terminal HRS sub-fragments—with a trend toward preferential antibody affinity for sub-fragments containing amino acids 90-150 (A3-A5). While reactivity to A3-A5 generally overlapped in different patient subsets, reactivity to A2 (aa 1-60) was frequently lower than that of larger subfragments encompassed by A3-A5. Patients with joint swelling had significantly increased reactivity to fragments A2 (p = 0.0036), A3 (p = 0.0015), A4 (p = 0.0014) and A5 (p = 0.0016) relative to patients without joint swelling. Patients with Raynaud’s also had significantly increased reactivity to fragments A2 (p = 0.0147), A3 (p = 0.0497), A4 (p = 0.0209) and A5 (p = 0.0225) compared to patients without Raynaud’s.
Conclusion: This work not only confirms that the amino terminal portion of HRS/Jo-1 contains an immunodominant B cell epitope, but also suggests that fine specificity mapping may provide useful biomarkers for different patterns and/or severity of organ involvement. More broadly, these results support the possibility that tissue-specific alterations in antigen presentation are linked to disease pathogenesis.
To cite this abstract in AMA style:LaConti J, Kippelen F, Aggarwal R, Ascherman DP. Correlations Between B Cell Epitope Specificity and Clinical Features in Patients with Jo-1 Antibodies and the Anti-Synthetase Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/correlations-between-b-cell-epitope-specificity-and-clinical-features-in-patients-with-jo-1-antibodies-and-the-anti-synthetase-syndrome/. Accessed June 1, 2023.
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