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The alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis
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  • Sergey Moiseev,
  • Jiwon Lee,
  • Anastasiia Zykova,
  • Nikolay Bulanov,
  • Pavel Novikov,
  • Eugeniy Gitel,
  • Mayra Bulanova,
  • Elizaveta Safonova,
  • Jae Shin,
  • Andreas Kronbichler,
  • D R W Jayne
Sergey Moiseev
Sechenov First Moscow State Medical University
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Jiwon Lee
Chungnam National University Hospital and College of Medicine
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Anastasiia Zykova
Sechenov First Moscow State Medical University
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Nikolay Bulanov
Sechenov First Moscow State Medical University
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Pavel Novikov
Sechenov First Moscow State Medical University
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Eugeniy Gitel
Sechenov First Moscow State Medical University
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Mayra Bulanova
Vladimir Clinical Hospital
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Elizaveta Safonova
Lomonosov Moscow State University
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Jae Shin
Yonsei University College of Medicine
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Andreas Kronbichler
Innsbruck Medical University
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D R W Jayne
Addenbrooke's Hospital
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Abstract

Objectives. We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Methods. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. Results. The median concentrations of MAC, C5a, C3a, and factor B were higher in active AAV patients (p<0.001). Achievement of remission was associated with reductions in C3a (p=0.005), C5a (p=0.035), and factor B levels (p=0.045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression, or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered in the meta-analysis. Plasma MAC, C5a, and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Conclusion. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

Peer review status:Published

14 Jun 2020Submitted to Clinical & Experimental Immunology
16 Jun 2020Submission Checks Completed
16 Jun 2020Assigned to Editor
16 Jun 2020Reviewer(s) Assigned
05 Jul 2020Review(s) Completed, Editorial Evaluation Pending
06 Jul 2020Editorial Decision: Revise Minor
12 Jul 20201st Revision Received
12 Jul 2020Review(s) Completed, Editorial Evaluation Pending
12 Jul 2020Editorial Decision: Accept
21 Jul 2020Published in Clinical & Experimental Immunology. 10.1111/cei.13498