Argonaute, Vault, and Ribosomal Proteins Targeted by Autoantibodies in Systemic Lupus Erythematosus.

Autor:	Moadab F; F. Moadab, MD, X. Wang, PhD, R. Najjar, MD, C. Lood, PhD, T. Mustelin, MD, PhD, Division of Rheumatology, University of Washington, Seattle, Washington, USA., Wang X; F. Moadab, MD, X. Wang, PhD, R. Najjar, MD, C. Lood, PhD, T. Mustelin, MD, PhD, Division of Rheumatology, University of Washington, Seattle, Washington, USA., Najjar R; F. Moadab, MD, X. Wang, PhD, R. Najjar, MD, C. Lood, PhD, T. Mustelin, MD, PhD, Division of Rheumatology, University of Washington, Seattle, Washington, USA., Ukadike KC; K.C. Ukadike, MD, Division of Rheumatology, University of Washington, Seattle, Washington, now with Renown Rheumatology, Department of Internal Medicine, Renown Health, and University of Nevada, Reno School of Medicine, Reno, Nevada, USA., Hu S; S. Hu, PhD, T. Hulett, PhD, CDI Laboratories, Baltimore, Maryland, USA, and Mayaguez, Puerto Rico., Hulett T; S. Hu, PhD, T. Hulett, PhD, CDI Laboratories, Baltimore, Maryland, USA, and Mayaguez, Puerto Rico., Bengtsson AA; A.A. Bengtsson, MD, PhD, Division of Rheumatology, Lund University, Lund, Sweden., Lood C; F. Moadab, MD, X. Wang, PhD, R. Najjar, MD, C. Lood, PhD, T. Mustelin, MD, PhD, Division of Rheumatology, University of Washington, Seattle, Washington, USA., Mustelin T; F. Moadab, MD, X. Wang, PhD, R. Najjar, MD, C. Lood, PhD, T. Mustelin, MD, PhD, Division of Rheumatology, University of Washington, Seattle, Washington, USA; tomas2@uw.edu.
Jazyk:	angličtina
Zdroj:	The Journal of rheumatology [J Rheumatol] 2023 Sep; Vol. 50 (9), pp. 1136-1144. Date of Electronic Publication: 2023 May 01.
DOI:	10.3899/jrheum.2022-1327
Abstrakt:	Objective: To expand, in an unbiased manner, our knowledge of autoantigens and autoantibodies in patients with systemic lupus erythematosus (SLE) and evaluate their associations with serological and clinical variables. Methods: Human proteome arrays (> 21,000 proteins) were screened with serum from patients with SLE (n = 12) and healthy controls (n = 6) for IgG and IgA binding. Top hits were validated with 2 cohorts of patients with SLE (cohort 1, n = 49; cohort 2, n = 46) and other rheumatic diseases by ELISA. Clinical associations of the autoantibodies were tested. Results: Ro60 was the top hit in the screen, and the 10 following proteins included 2 additional known SLE autoantigens plus 8 novel autoantigens involved in microRNA processing (Argonaute protein 1 [AGO1], AGO2, and AGO3), ribosomes (ribosomal protein lateral stalk subunit P2 and ovarian tumor deubiquitinase 5 [OTUD5]), RNA transport by the vault (major vault protein), and the immune proteasome (proteasome activator complex subunit 3). Patient serum contained IgG reactive with these proteins and IgA against the AGO proteins. Using the 95th percentile of healthy donor reactivity, 5-43% were positive for the novel antigens, with OTUD5 and AGO1 showing the highest percentages of positivity. Autoantibodies against AGO1 proteins were more prevalent in patients with oral ulcers in a statistically significant manner. IgG autoantibodies against AGO proteins were also seen in other rheumatic diseases. Conclusion: We discovered new autoantigens existing in cytosolic macromolecular protein assemblies containing RNA (except the proteasome) in cells. A more comprehensive list of autoantigens will allow for a better analysis of how proteins are targeted by the autoimmune response. Future research will also reveal whether specific autoantibodies have utility in the diagnosis or management of SLE. (Copyright © 2023 by the Journal of Rheumatology.)
Databáze:	MEDLINE
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