Ab1255 Serum C3/C4 Levels in Renal Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Predictors of Lung Disease and Worse Prognosis

Background: Complement activation, specially the alternative pathway, has been implicated in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This was further corroborated with the efficacy of Avacopan, a selective C5a receptor inhibitor used as a corticosteroids reduction strategy in the treatment of AAV 1. Low complement factor 3 (C3) levels without real hypocomplementemia are predictors of prognosis in AAV 2. Low C4 levels have not yet been associated with worst outcomes. Objectives: To evaluate the association between circulating C3 and C4 levels at diagnosis of AAV with clinical and biochemical features and with relevant outcomes: relapse, dialysis and death. Methods: We conducted a retrospective study including 63 patients with AAV with renal involvement followed between 2003-2023, with C3 and C4 levels measurements at diagnosis. Data was recorded from clinical registries. Patients were grouped according to the median C3 and/or C4 levels, as previously performed 2. Groups were compared using the chi-square test for categorical variables and non-parametric tests for continuous variables. We created a logistic regression model for the outcomes, adjusting for covariates. Results: Mean age at diagnosis was 61,1±13,4 years old and most patients had ANCA MPO specificity (69,8%, n=44). Only 3 patients had low C3 levels (Conclusion: Complement activation in AAV has been previously associated to renal outcomes, but our results also highlight a possible role of complement in the pathophysiology of lung disease. Low C4 levels were associated with higher relapse rates and faster progression to dialysis, revealing that C4 activation impacts outcomes in AAV and that both classic and alternative complement pathways are involved. Combining low C3 and/or C4 levels identified patients at higher risk of acute dialysis requirement, independently of renal function at admission. Further insights in the specific effects of C3/C4 are needed to stipulate the value of monitoring and targeting complement factors in AAV. REFERENCES: 1 Jayne, D.R.W., et al., Avacopan for the Treatment of ANCA-Associated Vasculitis. N Engl J Med, 2021. 384(7): p. 599-609. 2 Augusto, J.F., et al., Low Serum Complement C3 Levels at Diagnosis of Renal ANCA-Associated Vasculitis Is Associated with Poor Prognosis. PLoS One, 2016. 11(7): p. e0158871. Acknowledgements: NIL. Disclosure of Interests: None declared.