The alternative complement pathway in ANCA-associated
vasculitis: further evidence and a meta-analysis
Sergey Moiseev1,2*, Jiwon M. Lee3*,
Anastasiia Zykova1,2, Nikolai
Bulanov1, Pavel Novikov1, Eugeniy
Gitel1, Mayra Bulanova4, Elizaveta
Safonova2, Jae Il Shin5,6,7, Andreas
Kronbichler8,9, David R.W. Jayne9
1Tareev Clinic of Internal Diseases, Sechenov First
Moscow State Medical University, Moscow, Russia
2Lomonosov Moscow State University, Moscow, Russia
3Department of Pediatrics, Chungnam National
University Hospital and College of Medicine, Daejeon, Korea
4Vladimir Clinical Hospital, Vladimir, Russia
5Department of Pediatrics, Yonsei University College
of Medicine, Seoul, Korea
6Division of Pediatric Nephrology, Severance
Children’s Hospital, Seoul, Korea
7Institute of Kidney Disease Research, Yonsei
University College of Medicine, Seoul, Korea
8Department of Internal Medicine IV (Nephrology and
Hypertension), Medical University Innsbruck, Innsbruck, Austria
9Department of Medicine, University of Cambridge,
Cambridge, UK
Corresponding Authors:
Jae Il Shin, M.D., Ph.D. Address: Yonsei-ro 50, Seodaemun-gu, C.P.O. Box
8044, Department of Pediatrics, Yonsei University College of Medicine,
Seoul 03722, Republic of Korea. Tel.: +82-2-2228-2050; Fax:
+82-2-393-9118; E-mail:
shinji@yuhs.ac
Anastasiia Zykova, M.D., Ph.D. Address: Rossolimo, 11/5, Moscow, Russia.
Tareev Clinic of Internal Diseases, Sechenov First Moscow State Medical
University. E-mail: ansezy@gmail.com
* These authors contributed equally to this work
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.