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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/longitudinal-pattern-of-circulating-complement-activation-in-anca-vasculitis/