Background B cells are playing a major role in granulomatosis with polyangiitis (GPA, formerly known as Wegener’s disease). This is reflected by autoantibodies directed against neutrophil granular encymes (ANCA) as well as in the success of B cell depleting therapies. Whether mucosal plasma cells play a role in ENT-involvement is yet unknown. IgA-ANCA are found in about 30% of GPA patients and more often in patients with ENT-GPA (Kelley et al). For a better understanding of the possible role of plasma cells in GPA we analysed B cells subsets in the peripheral blood of patients and found major changes correlating with disease activity (BVAS).
Methods 18 patients with GPA (11 with active disease, 7 in remission) were analysed by flow cytometry and compared to 17 healthy donors and 6 patients with systemic sclerosis. Stainings for CD19, 20, 27, IgD, IgA and MHCII were performed and analysed by FlowJo-software. The study was approved by the Charité ethics committee and all patients signed informed consent. Statistical analysis was performed using GraphPadPrism.
Results : Marked differences (p = 0.0018) were found regarding the number and frequency of plasmablasts/plasma cells in patients with active disease (6.4 ± 5.06/µl) as compared to patients in remission (2.5 ± 1.6/µl) or healthy donors (2.3 ± 1.2/µl). In patients with GPA a significant higher number of the plasma cells produced IgA as compared to healthy controls (p = 0.0028). The same was true in patients with systemic sclerosis. So far, no difference regarding the IgA plasma cells in the blood was observed between patients with ENT-GPA and patients with systemic GPA (sGPA), while sGPA patients tend to have more plasma cells in the blood.
The number of plasma cells and IgA plasma cells correlate with disease activity (r = 0.9135, p<0.0001).
Conclusion The number of plasma cells in active GPA is increased. This implies a central role of plasma cells in the pathogenesis of GPA. A high frequency of these plasma cells is producing IgA, which could play a role in ENT-involvement. So far now diffenerce could be observed between ENT-GPA and sGPA but further studies and more detailed studies including the analysis of ENT biopsies are needed to further understand their role in disease pathogenesis.