SAT0268 COMPLEMENT ACTIVATION VIA ALTERNATIVE PATHWAY IN ANCA-ASSOCIATED VASCULITIS

Abstract

Background:There is increasing evidence that the complement system, in particular the alternative pathway, plays a crucial role in the pathogenesis of ANCA-associated vasculitis (AAV) [1]. Efficacy of C5a receptor antagonists indicates that chemoattraction mediated by C5a plays a key role in the inflammatory process observed in AAV [2]. Another promising research object are regulatory proteins such as factor B [3].Objectives:To study complement activation via the alternative pathway in patients with active ANCA-associated vasculitis.Methods:59 patients with newly diagnosed (n=35) or relapsing GPA or MPA (n=24) were enrolled in this prospective study. Median BVAS v.3 at the time of AAV onset was 16.5 (9.5; 20). In 28 patients activation of complement was reassessed during sustained remission (BVAS v.3 = 0) after a median of 16 months. Thirty six age-and gender-matched healthy volunteers comprised the control group. Levels of complement components (C3, C5, C3a, C5a, vitronectin, factor B and factor P) were measured by ELISA (Cloud Inc.). Data were not normally distributed, therefore, values are given as medians and IQRs and nonparametric statistical tests were used.Results:The concentrations of C5, C3, vitronectin and CFB were significantly higher in patients with active AAV than control group. There were no significant differences in the levels of factor P in patients with active AAV and control group (388000 (371960; 417150)) vs 416000 (400200; 437000), ng/ml, p >0.05) (Fig. 1).Fig 1.Concentration of complement components in patients with active AAV and healthy controls (*p<0.05)Serum level of C5a and C3a were higher in patients with active AAV than in healthy controls (22.9 (14.4; 33.0) vs 3.0 (0.35; 6.73), ng/ml, p<0.001; 21436 (11395; 21436) vs 1224.5 (798.5; 1947.7), ng/ml, p<0.001). Patients with active AAV had significantly higher MAC levels than healthy controls (24646 (15342; 46681) vs 3305.5 (2780.2; 3777.5), mAU/ml, p<0.001).The levels of complement components were similar in PR3-ANCA and MPO-ANCA disease, and severe and non-severe AAV. C5a/C5 and C3a/C3 ratios were not influenced by disease activity, severity or ANCA type.After immunosuppressive treatment concentrations of C5, C3, and their activated products, C5a, C3a significantly decreased (Fig. 2). However, concentrations of regulatory proteins such as factor B, factor P and vitronectin were unaffected. Interestingly, that there was no significant difference in MAC levels before and after immunosuppressive treatment (24646 (15342; 46681) vs 20057.4 (19709.3; 41477.6), mAU/ml, p=0.925).Fig 2.Concentration of complement components in patients with active disease and remission (*p<0.001)Conclusion:The complement system plays an important role in AAV. While treatment affects some component, some remain unchanged and are not dependent on AAV severity or ANCA serotype.