Abstract
Background and Aims
The diagnostic utility of ANCA antibodies in ANCA associated-vasculitis (AAV), antiproteinase 3 (PR3) and myeloperoxidase (MPO) testing is now undisputed, but the clinical utility of serial MPO/PR3 testing to predict relapses, remain controversial. The aim of this study was to analyze the relevance of serum MPO and PR3 antibody level assessment in the management of AAV. We sought to determine whether MPO and PR3 antibody levels correlated with renal disease activity, and whether an increase could predict a nephritis flare.
Method
Retrospective multicenter study including AAV-patients with renal involvement from 7 nephrology departments belonging to the Spanish Glomerular Study Group (GLOSEN). The main inclusion criteria were that MPO antibodies were detected by ELISA (Multiplex assay) and PR3 using chemioluminescence immunoassay. For statistical purpose a continuous variable were calculated, called delta MPO/PR3(ΔMPO y ΔPR3) that reflects change in antibodies levels 6 months before renal flare. Clinical data were recorded since complete remission of first nephritis diagnosis flare until second renal relapse.
Results
113 AAV-patients with pauci-inmune necrotizing glomerulonephritis were included, 59 (52.2%) women, mean age (64.3±14.8 years), 85 patients (75.2%) MPO-AAV and 28 (24.8%) PR3-AAV, after a mean follow-up of 5±4.8 years, 54 renal relapses occurred in 40 (52,6%) MPO-AAV patients and in 14 (57.1%) PR3-AAVpatients. Serum MPO levels were significant higher in relapser-patients compared with non- relapser patients, 3±1.2 months before nephritis relapse [(n=32) 19.2±12.2 IA vs (n=38) 3.2±5.1 IA, p<0.001)]. Δ MPO levels were significant higher in relapse-patients compared with non-relapser patients [(n=32) 8.3±12 IA vs (n=38) 0.9±3.1.1 IA, p=0.001). The discrimination value of the MPO antibody levels 3 months before renal relapse were established by means of a ROC curve: AUC of 0.82 (95% CI 0.73 to 0.92; p<0.001) and the MPO cut-off value predicting renal relapse were established in 8.3 IA. The discrimination value of the ΔMPO were established by means of ROC curve: AUC of 0.76 (95% CI 0.63 to 0.88; p<0.001), ΔMPO cut-off value were established in an increase of MPO levels of 3.7 IA. Serum PR3 levels were significant higher in relapser-patients 2.8±1.4 months before relapse [(n=14) 58.6±6.6 IA vs (n=7) 2.0±0.6 IA, p<0.001)] and Δ PR3 levels were significant higher in relapse-patients compared with non-relapser patients [(n=14) 57.5±28.5 IA vs (n=7) 0.8±0.2. IA, p<0.001)]. The discrimination value of the PR3 3 months before flare and Δ PR3 antibody levels were established by means of ROC curve: AUC 1.
Conclusion
Our results show that MPO antibodies, measured by Multiplex assay, could be a useful predictor of glomerulonephritis flare in AAV-patients. MPO levels 3 months before renal flare seems a good marker confirmed by ROC curve results, MPO cut-off value with the best sensitivity and specificity in predicting renal relapse was established in 8.3 IA. Δ MPO levels show that increase in titers ≥ 3.7 IA 6 months before renal flare, predict nephritis relapse However, PR3 antibodies are not a useful predictor marker, rise in antibodies level indicate renal vasculitis activity.
Pauci-immune necrotizing glomerulonephritis in a patient with ankylosing spondylitis
