Anti-myeloperoxidase and proteinase 3 antibodies for nephritis flare prediction in anti-neutrophil cytoplasmic antibody–associated vasculitis

Abstract

Background The value of myeloperoxidase and proteinase 3 antibodies titers in the assessment of renal disease activity and flare prediction in patients with ANCA-associated-vasculitis (AAV) is not well-known. Methods Retrospective study including 113 AVV patients with a renal biopsy-proven pauci-immune necrotizing glomerulonephritis from seven Spanish hospitals. The main inclusion criteria were assessment of MPO antibodies (MPOab) using multiplex flow immunoassay and PR3 antibodies (PR3ab) measurements using immunoassay chemiluminescence with an identical range of values for all participating centers. Results Serum MPOab, 3 ± 1.2 months before relapse, was higher in patients who relapsed (19.2 ± 12.2 vs 3.2 ± 5.1 AI, p < 0.001). The discrimination value of MPOab 3 months before renal relapse had an AUC of 0.82 (95%CI 0.73-0.92; p < 0.001). ΔMPOab (change in antibodies titration 6 months before relapse) was higher in patients who relapsed [8.3 ± 12 vs 0.9 ± 3.1 AI, p = 0.001) (AI; antibody index unit). The discrimination value of ΔMPO had an AUC of 0.76 (95%CI 0.63-0.88; p < 0.001). The positive predictive value of renal relapse in PR3 patients is 100% and the negative predictive value of renal relapse in patients with PR3 positive titers is 57.1%. Serum PR3ab was higher in patients who relapsed 2.8 ± 1.4 months before relapse (58.6 ± 24.6 vs 2.0 ± 0.6 AI, p < 0.001). Conclusions MPO antibody level monitorization using multiplex flow immunoassay and PR3 measurements using immunoassay chemiluminescence are useful and sensitive tools for the prediction of renal relapse in the follow-up of AAV patients with renal disease, and relevant surrogate markers of renal disease activity.

Remote self-collection of capillary blood using upper arm devices for autoantibody analysis in patients with immune-mediated inflammatory rheumatic diseases

“… 37 It would add valuable objective data to complement currently available remote PROs, such as electronic questionnaires 51 and wearable data. 52 Exact quantification of autoantibody levels is currently not clinically relevant for all IMRDs, however, increasing evidence exists for MPO, 9 PR3 8 9 and especially dsDNA, 7 and our study demonstrates clinical utility with very good agreement for PR3 (r=0.9818 (p<0.0001), mean bias −2.03%). In agreement with previous studies, 26 37 53 we did not observe a clinically significant effect of delayed sample processing and uncontrolled conventional mail postage.…”

“… 4 Similarly, serological biomarkers such as C reactive protein (CRP) are part of gold-standard composite scores to longitudinally monitor disease activity, such as the 28-joint Disease Activity Score-CRP 5 for RA and the Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) for spondyloarthritis. 6 Additionally, an increasing number of publications emphasise the value of autoantibody levels such as dsDNA, 7 proteinase 3 (PR3) 8 or myeloperoxidase (MPO) 9 as predictive surrogate parameters for disease activity and flares.…”

Anti-neutrophil cytoplasmic antibody patterns can predict clinical relapse in ANCA-associated vasculitis: overall population and subgroups

“…To minimise population heterogeneity (30), we analysed the risk factors for relapse in MPO-AAV patients separately, which showed that ANCA patterns were independent predictors of MPO-AAV relapse. Studies in the last decade have found that anti-MPO antibody levels are closely correlated with BVAS and disease sever- ity index, but the relationship between anti-PR3 antibody and disease activity has not been found (11,(31)(32)(33). Similarly, in vitro and in vivo experiments confirmed the pathogenicity of MPO-ANCA, but the convincing evidence of PR3-ANCA has not been reported to date (25,(34)(35)(36).…”