219. Anti-complement C5a receptor antibodies are decreased in ANCA-associated vasculitis and associated with relapse
Creators: name: Sebastian Klapa1, 2
name: Müller1, Antje
name: Koch2, Andreas
name: Kerstein-Staehle1, Anja
name: Wataru Kähler2,
name: Heidecke3, Harry
name: Lang4, Markus Huber
name: Nitschke5, Martin
name: Pitann1, Silke
name: Augustin1, Solveig
name: Karsten6, Christian
name: Riemekasten1, Gabriela
name: Lamprecht1, Peter
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background: </strong>Complement activation has been shown to play an important role in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) (1,2). Circulating proinflammatory anaphylatoxin C5a concentrations are increased and correlate with disease activity in AAV (3). Interaction of C5a with C5aR represents a proinflammatory amplification loop (1). Binding of C5a to its corresponding G protein-coupled receptor (C5aR/CD88) enhances the influx of neutrophils and their activation, leading to ROS generation and severe necrotizing of vascular walls (3). Blocking of C5aR is protective in a murine model of ANCA-induced necrotizing crescentic glomerulonephritis (4). In humans, recent studies demonstrate efficacy of the C5aR antagonist avacopan as glucocorticoid-sparing agent in AAV (5). The aim of the present study was to examine whether concentrations of anti-C3aR and anti-C5aR antibodies correlate with clinical findings and outcomes in AAV. <strong>Methods: </strong>Sera and plasma of AAV patients [granulomatosis with polyangiitis (GPA), n=82; microscopic polyangiitis (MPA), n=28], systemic lupus erythematosus (SLE, n=36) and healthy donors (HD, n=220) were measured by Elisa for circulating autoantibodies against complement receptors C3a (anti-C3aR), C5a (anti-C5aR) and plasma levels of C3a and C5a. Expression of C3aR and C5aR on T-cells was determined using flow cytometry. Clinical data were assessed at the time of serum sampling and during follow-up for 60 months. <strong>Results: </strong>Decreased concentrations of anti-C3aR and anti-C5aR antibodies were found in AAV compared with HD (figure 1a, p=0.0026; figure 1b, p≤0.0001). Whereas both anti-C3aR and anti-C5aR antibodies were decreased in GPA, anti-C3aR antibody levels were similar to HD in MPA (figure 1a, 1b). In particular, newly diagnosed GPA patients with high disease activity displayed the lowest levels of anti-C5aR antibodies (p=0.0007). C5a and anti-C5aR antibody concentration showed a negative correlation in GPA (r= -0.6831, p=0.0127). The frequency of C5aR expressing cells within the total CD4+ and CD8+ T-cell populations was increased in GPA compared to HD (10.76±2.55% <em>vs</em>. 3.44±0.68%, p=0.0021 and 9.74±2.10% <em>vs.</em> 4.11±0.92%, p=0.0198, respectively). Anti-C5aR antibody concentrations &lt;0.45U/ml were associated with an increased risk for relapse in AAV (fig.1c). <strong>Conclusions: </strong>Low concentrations of circulating anti-C5aR antibodies reflect disease activity and are associated with an increased risk for relapse in AAV. <strong>Disclosures:</strong> none <strong>Figure 1.</strong> Anti-C3aR and anti-C5aR antibody concentrations in AAV. A: Anti-C3aR antibody concentrations compared to HD, MPA, and SLE B: Anti-C5aR antibody concentrations compared to HD, MPA, and SLE. C: Anti-C5aR antibody concentrations &lt;0.45 U/I were associated with a higher relapse rate in AAV. <strong>A</strong> <strong>B</strong> <strong>C</strong>