Decreased concentrations of C5a complement receptor antibodies are associated with relapse in eosinophilic granulomatosis with polyangiitis (EGPA)

Complement activation via the alternative pathway with subsequent generation of the C5a complement fragment has an important role in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) pathophysiology .1 Binding of C5a to the G protein-coupled receptor (GPCR) C5a receptor 1 (C5aR1, CD88) boosts neutrophil activation and induces severe vessel necrosis in experimental myeloperoxidase-specific (MPO)-ANCA-induced glomerulonephritis .2 Moreover, the glucocorticoid-sparing oral C5aR antagonist avacopan improves disease control and renal recovery in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two major subgroups of AAV.3 Notably, serum concentrations of endogenous anti-GPCR antibodies targeting C3a and C5a complement receptors are decreased in GPA and MPA compared with healthy individuals. Lower concentrations of anti-C5aR antibodies, but not anti-C3aR antibodies, were associated with disease activity and relapse suggestive of C5aR as an immune checkpoint regulated by endogenous anti-C5aR antibodies in AAV .4 Similar to neutrophils, eosinophils constitutively display C5aR1 expression .5 As suggested by an earlier study showing increased C4 complement and CH50 serum concentrations, complement activation may also play a role in eosinophilic granulomatosis with polyangiitis (EGPA), the third and minor subgroup of AAV characterised by eosinophil-rich necrotising granulomatous inflammation and systemic small vessel vasculitis .6 Therefore, we were interested in examining anti-C3aR and anti-C5aR antibody concentrations and analysing their association with disease activity and relapse in EGPA.

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Klapa, S., Müller, A., Arnold, S., Koch, A., Staehle, A., Kaehler, W., Heidecke, H., Riemekasten, G., Karsten, C.M., Lamprecht, P., 2025. Decreased concentrations of C5a complement receptor antibodies are associated with relapse in eosinophilic granulomatosis with polyangiitis (EGPA). RMD Open 11, e005323. https://doi.org/10.1136/rmdopen-2024-005323
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