Low concentrations of C5a complement receptor antibodies are linked to disease activity and relapse in ANCA-associated vasculitis

To examine concentrations of circulating antibodies targeting C3a and C5a complement receptors in ANCA-associated vasculitis (AAV) and analyze their association with disease activity.Concentrations of antibodies against C3a and C5a complement receptors and plasma complement fragments C3a and C5a were determined in patients with AAV (n = 110; granulomatosis with polyangiitis [GPA, n = 82], microscopic polyangiitis [MPA, n = 28]), systemic lupus erythematosus as disease control (SLE, n = 36) and healthy donors (HD, n = 220). C3aR and C5aR expression by circulating neutrophils, monocytes and T cells was analyzed using flow cytometry. Clinical data were assessed at time of serum sampling and during follow-up for 60 months.In AAV, anti-C3aR and anti-C5aR antibodies were decreased (P = 0.0026 and ≤ 0.0001, respectively). In remission, anti-C3aR antibody concentrations rose to values comparable to HD, whereas anti-C5aR antibody concentrations did not. In GPA, C5a and anti-C5aR antibody concentrations inversely correlated with each other (r = -0.6831, P = 0.0127). In newly diagnosed GPA, decreased concentrations of anti-C5aR antibodies but not anti-C3aR antibodies were associated with disease activity (P = 0.0009). Moreover, low anti-C5aR antibodies were associated with relapse in GPA (HR: 3.54, P = 0.0009) and MPA (HR: 4.41, P = 0.0041). The frequency of C5aR-expressing cells within T cell populations was increased in GPA (CD4+ T cells: P = 0.0021; CD8+ T cells: P = 0.0118), but not in MPA.Low concentrations of anti-C5aR antibodies reflect disease activity and are associated with an increased risk for relapse in AAV. This article is protected by copyright. All rights reserved.