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Argonaute, Vault, a...
Argonaute, Vault, and Ribosomal Proteins Targeted by Autoantibodies in Systemic Lupus Erythematosus
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- Moadab, Fatemeh (författare)
- University of Washington
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- Wang, Xiaoxing (författare)
- University of Washington
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- Najjar, Rayan (författare)
- University of Washington
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- Ukadike, Kennedy C. (författare)
- University of Washington
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- Hu, Shaohui (författare)
- CDI Laboratories
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- Hulett, Tyler (författare)
- CDI Laboratories
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- Bengtsson, Anders A. (författare)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Lood, Christian (författare)
- University of Washington
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- Mustelin, Tomas (författare)
- University of Washington
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(creator_code:org_t)
- 2023
- 2023
- Engelska 9 s.
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Ingår i: The Journal of rheumatology. - 0315-162X. ; 50:9, s. 1136-1144
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Nyckelord
- autoantibodies
- proteins
- systemic lupus erythematosus
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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