AB0444 Role of plasma cell analysis as a biomarker for disease activity in patients with granulomatosis with polyangiitis. (23rd January 2014)

• Record Type: Journal Article
• Authors: Hoyer, B. F.; Taddeo, A.; Rothkegel, M.; Schneider, U.; Burmester, G.-R.; Radbruch, A.; Hiepe, F.
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 3(2013)
• Page Start: A924
• Page End: A924
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-eular.2766
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: B cells are important players in granulomatosis with polyangiitis (GPA) as suggested by the presence of autoantibodies reacting with specific neutrophil granular enzymes ANCA) in a vast majority of patients as well as the success of B cell depleting therapies in GPA. Renal manifestations in GPA are considered to be directly ANCA – mediated whereas the granulomatous inflammation appears to be mediated by CD4 T cells. Objectives: For a better understanding of the possible role of B cells in ANCA-associated vasculitis we analyzed the B cell subsets in the peripheral blood of patients with GPA and found marked changes correlating with disease activity as measured by the BVAS (Birmingham vasculitis activity score) as well as ANCA-levels. Methods: 17 patients with GPA (10 with active disease, 7 with inactive disease) were analyzed by flow cytometry as compared to 20 healthy donors. Staining for CD27, CD20, CD19, MHCII, CD3, 4 and 8 was analyzed using flowjo software. Statistical analysis was performed using graph pad prism, and p-values of < 0, 05 were considered as significant. The ethics committee of the Charité approved the study, and all patients had signed informed consent. Results: Marked differences (p=0, 0018) could be observed in plasma cell counts as well as frequencies in GPA patients (6, 5 ±5, 06/µl) with a BVAS-score > 0 as compared to those with a BVAS-score =0 (2, 5± 1, 6/µl) or healthy persons (2, 3±1, 15/µl). Plasma cell numbers as well as the frequency of plasma cells within all B cells correlated with the BVAS (r= 0, 91, p<0, 0001) as well as the ANCA-level in the serum (r= 0, 83, p=0, 0013). No significant differences could be observed for naive and memory B cells or the overall B cell numbers as compared to healthy donors. Regarding T cells, there was a significant reduction of CD3 (p=0, 01) and CD4 T (p=0, 012) cells in patients with active GPA as compared to patients in remission, whereas CD8 T cells did not show any significant changes. Conclusions: Plasma cell numbers are increased in patients with active GPA which implies a role for plasma cell mediated effects in active GPA. Presumably, their main role is the production of autoantibodies, but also cytokine production. Independent of their direct contribution to the disease, they may serve as a biomarker of disease activity as they highly correlate with the BVAS. References: Hoyer et al, ARD 2012 Disclosure of Interest: None Declared