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Complement activation prior to symptom onset in myeloperoxidase ANCA-associated vasculitis but not proteinase 3 ANCA associated vasculitis: a Swedish biobank study
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 Immunology, Genetics & Pathology, Uppsala University, Uppsala, Sweden.
Department of Clinical Sciences/Rheumatology, Lund University, Lund, Sweden; Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
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2022 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 51, no 3, p. 214-219Article in journal (Refereed) Published
Abstract [en]

Objective: Increased soluble levels of complement effectors have been demonstrated in active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but the timing of complement activation in the autoimmune inflammation remains elusive. This study investigated whether the complement system is activated before onset of symptoms in AAV.

Method: The Swedish National Patient Register and Cause of Death register were linked to registers of five biobanks to identify individuals sampled before AAV symptom onset. Diagnosis of AAV and time-point for symptom onset were confirmed by reviewing medical records. We identified 64 presymptomatic individuals with serum samples > 1 month < 10 years from AAV symptom onset and 122 matched controls. Complement factors (C2, C5) and activation markers (C5a, C4b) were measured using Luminex technology.

Results: Presymptomatic individuals had higher levels of C5 up to 6.5 years before symptom onset, compared with controls [median (IQR) 80.7 (131.9) vs 46.6 (63.4) µg/mL, p = 0.05]. Levels of C5a increased significantly during the pre-dating time (p = 0.033) until symptom onset. The complement levels were significantly higher in presymptomatic myeloperoxidase (MPO)-ANCA+ individuals versus MPO-ANCAand proteinase-3-ANCA+ individuals. C5 was significantly increased in cases with renal involvement at diagnosis versus controls (p = 0.022), whereas levels of both C5 and C5a were significantly increased in presymptomatic individuals diagnosed with microscopic polyangiitis after onset compared with controls (C5: p = 0.027; C5a: p = 0.027).

Conclusion: Activation of the complement system is an early event in the pathogenesis of AAV and is mainly associated with MPO-ANCA+ AAV and with microscopic polyangiitis.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2022. Vol. 51, no 3, p. 214-219
National Category
Rheumatology and Autoimmunity
Research subject
rheumatology
Identifiers
URN: urn:nbn:se:umu:diva-192169DOI: 10.1080/03009742.2021.1989814ISI: 000744923100001PubMedID: 35048784Scopus ID: 2-s2.0-85123416847OAI: oai:DiVA.org:umu-192169DiVA, id: diva2:1634638
Available from: 2022-02-03 Created: 2022-02-03 Last updated: 2022-07-08Bibliographically approved

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Johansson, LindaBerglin, EwaRantapää-Dahlqvist, Solbritt

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