Membrane expression of neutrophil proteinase 3 (PR3) is associated with relapse in PR3-ANCA related vasculitis
© BioMed Central Ltd 2002
Received: 15 January 2002
Published: 4 February 2002
The highly specific presence in serum of autoantibodies directed against intracellular neutrophil proteins such as PR3 (PR3-ANCA) suggests a pathophysiological role of these autoantibodies in patients with necrotizing small vessel vasculitis. A stable but interindividually highly variable membrane expression of PR3 has been found on resting neutrophils. We hypothesized that, in patients with PR3-ANCA related vasculitis, a higher expression of PR3 on neutrophil membrane would lead to more interaction with PR3-ANCA and could thereby influence the extent or course of the disease.
PR3 expression on unstimulated isolated neutrophils from patients with PR3-ANCA related vasculitis was determined by FACS analysis using anti-PR3 murine mAb 12.8. Patients were divided according to the distribution of neutrophil membrane PR3 in 3 groups: low, bimodal, and high. Disease extent at diagnosis was scored with the Birmingham Vasculitis Activity Score (BVAS). Actuarial relapse-free survival was calculated from diagnosis to the first relapse and compared between groups with the logrank test.
89 patients (age 49 ± 16.6; 47 male/42 female) with PR3-ANCA related vasculitis followed at our department were included. At diagnosis, renal involvement was present in 52(58%) and pulmonary involvement in 49 (55%) patients, BVAS was 23 ± 10.5. During follow-up (81 ± 67 months) 50 patients had one or more relapse. Age at diagnosis, organ involvement and BVAS at diagnosis were not different between patients with low (n = 32), bimodal (n = 26), and high (n = 31) neutrophil membrane PR3 expression. However, median relapse-free survival was 104.5 months in patients with low PR3 expression as compared to 36.6 and 30.8 months in patients with bimodal and high PR3 expression, respectively (P = 0.023). Clinical manifestations at first relapse of vasculitis were not different between these groups.
The level of individual PR3 expression on resting neutrophils is significantly associated with risk for relapse in patients with PR3-ANCA associated vasculitis, but not with disease extent or manifestations at diagnosis or relapse. These data support the hypothesis that interaction in vivo of ANCA with PR3 expressed on neutrophil membrane plays a role in the pathophysiology of PR3-ANCA related vasculitis.