LAUSR

Background In antineutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV), involvement of complements, especially alternative pathway of complement, has been reported in researches using mouse models. In human, while some studies have identified levels of C3 as a renal prognostic factor, entire complement factors in alternative pathway have not been evaluated. Objectives To evaluate complement profiles of AAV patients at diagnosis and at 6 months after treatments (Month 6). Methods In total, 91 incident cases of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) based on the European Medicines Agency algorithm were enrolled. They are a part of participants of the Japanese nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions (RemIT-JAV-RPGN). Multiplex complement bead assays to measure levels of C1q, C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C9, Factor D, Factor I, MBL, factor B, factor H, and properdin were performed using preserved sera at diagnosis and at Month 6. We compared complement levels at diagnosis of AAV patients with those of age- and sex-matched healthy donors, and compared those of the AAV patients at diagnosis and Month 6. Results Seventy-two of 91 patients had serum both at baseline and Month 6. Compared with healthy donors, GPA patients had significantly higher levels of C2, C5a, and Factor B, and significantly lower levels of C3b/iC3b, C4b, and properdin. MPA patients had significantly higher levels of C2 and Factor D, and significantly lower levels of C3b/iC3b, C4, C5, Factor H, and properdin (table 1). At baseline, GPA had significantly higher levels of C4, Factor B and Factor H, and had significantly lower levels of C4b and Factor D compared to MPA. There are no significant differences in levels of C3, C5, Factor D, MBL, and properdin using Wilcoxon signed-rank test between at diagnosis and Month 6 both in GPA and MPA. Factor I significantly decreased at Month 6 only in GPA. Other complement factors significantly decreased at Month 6 both in GPA and MPA.Abstract THU0463 – Table 1 Complement profiles of patients with AAV at baseline and healthy donors GPA (median) MPA (median) HD (median) GPA vs. MPA GPA vs. HD MPA vs. HD C1q, ng/mL 1 04 220 96 890 1 08 242 N.S. N.S. N.S. C2, ng/mL 50 181 54 422 18 610 N.S. p<0.05 p<0.05 C3, ng/mL 1265500 1371550 1416900 N.S. N.S. N.S. C3b/iC3b, ng/mL 10433000 11066000 17364500 N.S. p<0.05 p<0.05 C4, pg/mL 3 10 020 2 66 554 3 08 085 p<0.05 N.S. p<0.05 C4b, ng/mL 18 064 27 740 31 287 p<0.05 p<0.05 N.S. C5, ng/mL 30 014 27 805 32 015 N.S. N.S. p<0.05 C5a, pg/mL 7783 6592 4836 N.S. p<0.05 N.S. C9, ng/mL 6934 5905 6742 N.S. N.S. N.S. Factor D, ng/mL 5335 7706 5658 p<0.05 N.S. p<0.05 Factor I, ng/mL 29 917 25 633 25 653 N.S. N.S. N.S. MBL, ng/mL 3583 3638 3023 N.S. N.S. N.S. Factor B, ng/mL 2 54 961 1 80 045 2 12 153 p<0.05 p<0.05 N.S. Factor H, ng/mL 2 58 187 2 28 238 2 95 480 p<0.05 N.S. p<0.05 Properdin, ng/mL 18 794 19 665 32 521 N.S. p<0.05 p<0.05 GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; HD, health donor. Conclusions We found some differences in complement factors among GPA, MPA, and healthy donors. There were no differences of levels of C3, C5, Factor D, and properdin, which suggested involvements of alternative pathway, both in GPA and MPA between at diagnosis and Month 6. Disclosure of Interest None declared