Vasculitis & polymyalgia rheumatica
Association of C4d with disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis: evidence for classical/lectin complement pathway activation
Authors' conclusion
The specific C4d assay revealed activity in the classical/lectin complement pathway in AAV, which reflected general disease activity, but was not associated specifically with kidney involvement.
Study context
- Population
- Patients with active AAV (GPA or MPA; 24 PR3-ANCA, 16 MPO-ANCA positive; 33 with kidney involvement) and population-based controlsfollow-up sample in 24
- Participants
- 40 vs 20
- Comparison
- Active AAV vs population-based controls
- Active AAVn = 40
- Controlsn = 20reference
- Outcome
- Plasma C4d (complement activation fragment) in association with AAV activity
Methodological detailspopulation-based controls, follow-up sample after induction therapy, Plasma C4d by ELISA (cleavage-specific epitope); C4 and soluble terminal complement complex (sTCC) by ELISA; HLA-DRB1 typing
- Population-based controls
- Follow-up sample after induction therapy
- Plasma C4d by ELISA (cleavage-specific epitope); C4 and sTCC by ELISA; HLA-DRB1 typing
Main finding
As reported in the abstract
C4d, sTCC levels and C4d/C4 ratio, active AAV vs controls
- Higher C4d in active AAV than controls
- p < 0.001
- Higher sTCC in active AAV than controls
- p = 0.004
- Higher C4d/C4 ratio in active AAV than controls
- p < 0.001
Observational data: associations, not effects.
Further findings
Change from active disease to remission · after induction therapy (median 6 months)
- C4d decreased
- P = 0.010
- sTCC decreased
- P = 0.009
- C4d/C4 ratio decreased
- P = 0.011
- 24 with follow-up sample, 20 in remission
C4d in remission vs population-based controls
- C4d remained higher in remission than controls
- P = 0.026
Active PR3-ANCA vs MPO-ANCA patients
- Higher C4d in PR3-ANCA
- P = 0.001
- Higher C4d/C4 ratio in PR3-ANCA
- P = 0.007
Active AAV with vs without kidney involvement
- Lower C4d with kidney involvement
- P = 0.04
Kidney biopsies
- C4d levels and C4d/C4 ratio correlated positively with percentage of normal glomeruli
- Immunohistochemistry negative for C4d
Original publication
Association of C4d with disease activity in anti-neutrophil cytoplasmic antibody-associated vasculitis: evidence for classical/lectin complement pathway activation. Arthritis Res Ther. Published 5 March 2025. doi:10.
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