Eveline Wu1, Elizabeth McInnis2, Sarah Lewis2, Mary Collie2, Lauren Blazek2, Kristin Kennedy2, Yichun Hu2, Susan Hogan2, Candace Henderson2, Caroline Poulton2, Dhruti Chen2, Vimal Derebail2, J Charles Jennette3, Ronald Falk2 and Donna Bunch2, 1University of North Carolina, Chapel Hill, NC, 2UNC Kidney Center, The University of North Carolina Chapel Hill, Chapel Hill, NC, 3Department of Pathology and Laboratory Medicine, The University of North Carolina Chapel Hill, Chapel Hill, NC
Background/Purpose: Evidence is accumulating that alternative complement pathway activation is important in ANCA vasculitis pathogenesis. Our group was the first to show that complement activation occurs in both MPO-ANCA and PR3-ANCA vasculitis1. Objectives for this study were to investigate complement activation in a longitudinal cohort with ANCA vasculitis and evaluate associations between complement activation measures and clinical characteristics.
Methods: Subjects included 33 healthy controls and 31 ANCA vasculitis patients (11 MPO-ANCA, 20 PR3-ANCA) with paired samples obtained during active disease and remission. Active disease was defined as BVAS >3, and disease remission as BVAS=0 without disease activity within 3 months. Levels of Bb, C3a, C5a, sC5b-9, and properdin in plasma were measured by ELISA as described previously1 and median values reported. Data were analyzed with a paired signed-rank test. A power calculation based on prior data deemed 19 MPO-ANCA and PR3-ANCA patients each were needed; therefore, MPO-ANCA vasculitis patients were not analyzed separately due to small sample size2.A p-value of < 0.05 was considered statistically significant.
Results: Of the 31 ANCA vasculitis patients, 61% were male and median age was 53 years which were similar to healthy controls. Considering all ANCA vasculitis patients, levels of Bb (0.78 vs. 0.74 µg/mL), C3a (104.69 vs. 61.04 ng/mL), C5a (10.33 vs. 7.42 ng/mL), sC5b-9 (191.52 vs. 128.52 ng/mL) were significantly higher and levels of properdin (15.88 vs. 18.18 µg/mL) significantly lower during active disease compared to remission. Among PR3-ANCA vasculitis patients, levels of Bb (0.78 vs. 0.66 µg/mL), C3a (121.30 vs. 52.01 ng/mL), C5a (10.84 vs. 7.06 ng/mL), sC5b-9 (242.53 vs. 123.60 ng/mL) were significantly higher and levels of properdin (14.53 vs. 18.12 µg/mL) significantly lower during active disease compared to remission. Evaluating patients by organ manifestations, levels of Bb (0.81 vs. 0.66 µg/mL), C3a (109.53 vs. 65.16 ng/mL), C5a (10.13 vs. 7.78 ng/mL), and sC5b-9 (202.69 vs. 147.04 ng/mL) were significantly higher during active disease compared to remission in the 22 patients with renal involvement during active disease.
Conclusion: Complement activation occurs in ANCA vasculitis, and the activation profile differs by disease activity with higher Bb, C3a, C5a, and sC5b-9 levels and lower properdin levels during active disease compared to remission in our longitudinal cohort. PR3-ANCA vasculitis patients had a similar complement activation profile during active disease. The contribution of complement activation may differ by organ affected with higher Bb, C3a, C5a, and sC5b-9 levels in ANCA vasculitis patients with kidney involvement during active disease.
Disclosures: E. Wu, Pharming Healthcare Inc, AstraZeneca, Bristol-Myers Squibb(BMS), Janssen; E. McInnis, Fisher Scientific, Chemocentryx, Vertex, travere therapeutics; S. Lewis, None; M. Collie, None; L. Blazek, None; K. Kennedy, None; Y. Hu, None; S. Hogan, None; C. Henderson, None; C. Poulton, None; D. Chen, None; V. Derebail, Merck/MSD, Novartis, Forma Therapeutics, Bayer, UpToDate, Travere; J. Jennette, None; R. Falk, None; D. Bunch, None.
