Mass spectrometry-based identification of new anti-Ly and known antisynthetase autoantibodies. - Université de Lille Accéder directement au contenu
Article Dans Une Revue Annals of the Rheumatic Diseases Année : 2022

Mass spectrometry-based identification of new anti-Ly and known antisynthetase autoantibodies.

Résumé

Objectives To discover new and detect known antisynthetase autoantibodies (ASAs) through protein immunoprecipitation combined with gel-free liquid chromatography-tandem mass spectrometry (IP-MS). Methods IP-MS was performed using sera of individuals showing features of antisynthetase syndrome (ASyS) without (n=5) and with (n=12) previously detected ASAs, and healthy controls (n=4). New candidate aminoacyl-tRNA-synthetase (ARS) autoantigens identified through unbiased IP-MS were confirmed by IP-western blot. A targeted IP-MS assay for various ASA specificities was developed and validated with sera of patients with known ASAs (n=16), disease controls (n=20) and healthy controls (n=25). The targeted IP-MS assay was applied in an additional cohort of patients with multiple ASyS features or isolated myositis without previously detected ASAs (n=26). Results Autoantibodies to cytoplasmic cysteinyl-tRNA-synthetase (CARS1) were identified by IP-MS and confirmed by western blot as a new ASA specificity, named anti-Ly, in the serum of a patient with ASyS features. Rare ASAs, such as anti-OJ, anti-Zo and anti-KS, and common ASAs could also be identified by IP-MS. A targeted IP-MS approach for ASA detection was developed and validated. Application of this method in an additional cohort identified an additional patient with anti-OJ autoantibodies that were missed by line and dot immunoassays. Discussion CARS1 is the dominant cognate ARS autoantigen of the newly discovered anti-Ly ASA specificity. Rare and common ASA specificities could be detected by both unbiased and targeted IP-MS. Unbiased and targeted IP-MS are promising methods for discovery and detection of autoantibodies, especially autoantibodies that target complex autoantigens.
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Dates et versions

hal-04521525 , version 1 (26-03-2024)

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Jean-Baptiste Vulsteke, Rita Derua, Sylvain Dubucquoi, Frédéric Coutant, Sébastien Sanges, et al.. Mass spectrometry-based identification of new anti-Ly and known antisynthetase autoantibodies.. Annals of the Rheumatic Diseases, 2022, Annals of the Rheumatic Diseases, 82 (4), ⟨10.1136/ard-2022-222686⟩. ⟨hal-04521525⟩
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