Meta-analysis
Literature search and study selection. We performed a PubMed, EMBASE, and SCOPUS search to identify eligible articles. A forward search of the retrieved articles was performed and ‘google scholar’ was also assessed to screen for non-indexed publications. The last search was performed on December 12th, 2019. The search terms included: “ANCA vasculitis” OR “ANCA-associated vasculitis” OR “antineutrophil cytoplasmic antibody vasculitis” OR “AAV” AND complement. Publications were screened first by title, second by abstract, and finally by full-text, based on our eligibility criteria.
Inclusion and exclusion criteria. We included cross-sectional or longitudinal studies, which compared plasma levels of complement factors in patients with AAV and healthy controls. We excluded studies that have measured complement levels in the urine, other body fluids or biopsy specimens. The exclusion criteria also included review articles, case reports, and animal experiments.
Data extraction and outcome. Data extraction was carried out as recommended by the Cochrane handbook, and included authors, year of publication, study design, participants, demographic characteristics, and measurement of serum complements.
Quality assessment. This meta-analysis was conducted and reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement (Supplementary table S1). Risk of bias of individual studies at the outcome level was assessed by using the Newcastle-Ottawa scale. The scoring was performed independently by two researches (Lee JM and Shin JI) (Supplementary table S2).
Statistical analysis and evaluation of heterogeneity and publication bias. In the meta-analysis, the standard mean difference (SMD) method and corresponding 95% confidence intervals (CIs) were used to compare complement levels (mean±SD). Random effect models were used because of heterogeneity of the included studies. We assessed the heterogeneity of the studies by the Cochran Q test, and P -value of <0.1 was considered significant. The inconsistency across the studies was also measured by I2 metric, as a measure of the percentage of total variation across the studies because of the heterogeneity. I2 values of <25, 25-75 and >75% considered to represent low, moderate, and high levels of heterogeneity, respectively. Publication bias of each article was estimated by inspecting funnel plot. All analyses were conducted using RevMan 5.3.