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Protein profiling in presymptomatic individuals separates myeloperoxidase-antineutrophil cytoplasmic antibody and proteinase 3-antineutrophil cytoplasmic antibody vasculitides
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Department of Clinical Sciences/Rheumatology, Lund University, Lund, Sweden, and Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.ORCID iD: 0000-0003-1524-0851
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2023 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 75, no 6, p. 996-1006Article in journal (Refereed) Published
Abstract [en]

Objective: Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into the molecular processes underlying the disease, we examined biomarkers in blood samples collected prior to symptom onset.

Methods: The National Patient Register and Cause of Death register were searched for AAV-related International Classification of Diseases, Ninth Revision and Tenth Revision codes and linked to the registers from 5 biobanks. Eighty-five AAV patients with samples predating symptom onset of AAV were identified. For each case of AAV, 2 matched controls were included. Proteinase 3 (PR3)–ANCA and myeloperoxidase (MPO)–ANCA expression levels were analyzed using enzyme-linked immunosorbent assays. Using an Olink Inflammation panel, 73 of 92 proteins were included after quality control. Data were replicated in a second cohort of 48 presymptomatic individuals and 96 controls.

Results: Of the 20 proteins with the lowest P values in the original cohort, 7 were replicated in the second cohort and 5 proteins were found to be significant between the groups in a meta-analysis. Eleven different pathways were identified in network enrichment analyses and were found to be significant in both cohorts. Stratification of samples obtained ≤5 years before symptom onset showed significant levels of CCL23, vascular endothelial growth factor A, and hepatocyte growth factor, which were also increased at borderline significant levels in the replication cohort (interleukin-6 was found to be significantly increased in the replication cohort). In presymptomatic AAV patients, 6 proteins were associated with MPO-ANCA positivity, and 7 proteins were associated with PR3-ANCA positivity.

Conclusion: To our knowledge, this is the first study to identify protein markers preceding symptom onset in AAV patients. These findings set the stage for further research into the underlying cellular and molecular mechanisms in the pathogenesis of AAV and the diversification of patients into PR3-ANCA+ and MPO-ANCA+ subphenotypes. (Figure presented.).

Place, publisher, year, edition, pages
2023. Vol. 75, no 6, p. 996-1006
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-211991DOI: 10.1002/art.42425ISI: 000967341700001PubMedID: 36533851Scopus ID: 2-s2.0-85147033853OAI: oai:DiVA.org:umu-211991DiVA, id: diva2:1782122
Funder
Swedish Research Council, 2018-02551Stiftelsen Konung Gustaf V:s 80-årsfondUmeå UniversityRegion VästerbottenAvailable from: 2023-07-12 Created: 2023-07-12 Last updated: 2023-07-12Bibliographically approved

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Brink, MikaelBerglin, EwaLundquist, AndersLejon, KristinaRantapää-Dahlqvist, Solbritt

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