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Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis: a case-control study
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Department of Clinical Sciences/Rheumatology, Lund University, Lund, Sweden; Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
Department of Medical Biochemistry and Microbiology, and Medical Sciences, Uppsala University, Uppsala, Sweden.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
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2021 (English)In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 117, article id 102579Article in journal (Refereed) Published
Abstract [en]

Objectives: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed.

Methods: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point for symptom onset were confirmed by reviewing 504 case-record. Eighty-five AAV cases (34 males, 51 females) with samples >1 month < 10 years from AAV symptom onset and two controls matched for sex, age, and sampling time for each case were included. Samples were screened using ELISAs for ANCA and further analysed for PR3-or MPO- specificities.

Results: In ANCA-screen 35.7% of the pre-symptomatic cases and 3.5% of controls tested positive (p < 0.01). 26.2% of the cases were PR3-ANCA+ and 10.7% MPO-ANCA+. Median (Q1-Q3) predating time for PR3-ANCA+ was 2.7 (0.3–7.7) years and MPO-ANCA+ 2.0 (0.9–3.5) years. PR3-ANCA was demonstrated in samples up to nine years before symptom onset. At symptom onset predating PR3-ANCA+ cases were younger than PR3-ANCA- (P < 0.01), and MPO-ANCA+ were older than MPO-ANCA- (p < 0.05). Predating MPO-ANCA+ cases vs. MPO-ANCA- and vs. PR3-ANCA+ cases had more often at symptoms onset manifestations from lungs, kidneys or peripheral nervous system (p < 0.01 and p < 0.05, respectively).

Conclusion: The PR3-and MPO-ANCAs are present years before AAV symptom onset and represent distinct diseases.

Place, publisher, year, edition, pages
Elsevier, 2021. Vol. 117, article id 102579
Keywords [en]
AAV, GPA, MPA, MPO-ANCA, PR3-ANCA, Predate symptom onset
National Category
Rheumatology and Autoimmunity Urology and Nephrology
Identifiers
URN: urn:nbn:se:umu:diva-212005DOI: 10.1016/j.jaut.2020.102579ISI: 000614250900003PubMedID: 33340843Scopus ID: 2-s2.0-85097887786OAI: oai:DiVA.org:umu-212005DiVA, id: diva2:1782052
Funder
Swedish Research Council, 2018-02551Stiftelsen Konung Gustaf V:s 80-årsfondSwedish Rheumatism AssociationUmeå UniversityAvailable from: 2023-07-12 Created: 2023-07-12 Last updated: 2023-07-12Bibliographically approved

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Berglin, EwaJohansson, LindaEriksson, CatharinaRantapää-Dahlqvist, Solbritt

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