Abstract
ObjectivesAn important limitation in granulomatosis with polyangiitis (GPA) is the lack of disease activity markers. Immunoglobulin G4-positive (IgG4+) B cells and plasma cells are implicated in the pathogenesis of GPA. We hypothesized that the presence of these cells in peripheral blood could serve as disease activity parameter in GPA.MethodsWe included 35 proteinase 3-antineutrophil cytoplasmic antibodies-positive patients with GPA in a cross-sectional study. Active disease was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 3 (n = 15), remission as BVAS of 0 (n = 17), and low disease activity (LDA) as BVAS of 1–2 and clinical remission (n = 3). Healthy subjects (n = 10), patients with systemic lupus erythematosus (n = 24), and patients with rheumatoid arthritis (n = 19) functioned as control subjects. An additional longitudinal study was performed in ten patients with GPA. Using a validated qPCR test, we measured the IgG4:IgG RNA ratio in all groups and compared the results with known biomarkers.ResultsThe median qPCR score was higher in active GPA (21.4; IQR 12.1–29.6) than in remission/LDA (3.3; IQR 1.6–5.6) (Mann-Whitney U test, p < 0.0001) and outperformed other known disease activity parameters in detecting activity. A cutoff qPCR score of 11.2% differentiated active disease from remission/LDA accurately (AUC 0.993). The qPCR test correlated well with the BVAS (Spearman r = 0.77, p < 0.0001). In the longitudinal study, a decrease in BVAS correlated with qPCR score reduction (paired t test, p < 0.05).ConclusionsThe IgG4:IgG RNA ratio in GPA accurately distinguishes active disease from remission and correlates well with disease activity in these single-center studies. If these results are confirmed in larger longitudinal studies, this test might help to steer treatment decisions in patients with GPA.
Highlights
Granulomatosis with polyangiitis (GPA), formerly called Wegener’s disease, is a hallmark form of primary small vessel vasculitis
In immunoglobulin G subtype 4 (IgG4)-related disease (IgG4-RD), a multiorgan disease known for high IgG4+ plasma cell infiltration in tissue, we recently demonstrated that the presence of IgG4+ B-cell receptor (BCR) clones in blood can serve as a diagnostic and disease activity biomarker [18]
The symptoms scored in the Birmingham Vasculitis Activity Score (BVAS) per active disease and low disease activity (LDA) subject are shown in Additional file 1: Table S1
Summary
Granulomatosis with polyangiitis (GPA), formerly called Wegener’s disease, is a hallmark form of primary small vessel vasculitis. In GPA, the disease activity often fluctuates over time, making titration of therapy challenging [1]. Both disease activity and immunosuppressive therapies cause morbidity and mortality. Instruments measuring disease activity, such as the Birmingham Vasculitis Activity Score (BVAS), have provided a solution and have been validated [10, 11]. They require that a clinician is convinced that symptoms scored are attributable to vasculitis activity and not to clinical mimics such as infections.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
