Session Title: Vasculitis - Poster II: ANCA-Associated Vasculitis
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are both anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV), but differ in clinical presentation. Anti-myeloperoxydase (MPO)-ANCA were demonstrated to be pathogenic in mice, whereas proteinase 3 (PR3) itself is responsible for disruption of immune silencing in GPA rather than anti-PR3-ANCA. Perturbations in lymphocyte homeostasis associated with these abnormalities could differ between both conditions.
Methods: We analyzed the phenotypic characteristics of lymphocyte subsets in peripheral blood of 32 consecutive GPA patients and 8 MPA patients with active disease and 22 healthy controls (HC). Using flow cytometry we studied the expression of activation and inhibitory markers, cytokine receptors and inflammatory cytokines in B cells, and main effector (i.e. Th1, Th2, Th9 and Th17 cells) and regulatory T cell (Tregs) subsets.
Results: B cell analyses revealed that B cell subsets were similar between GPA and HC. In contrast, MPA patients had significantly more IgD+/CD27– naive B cells (69.1% vs. 50.7%, P=0.04) and less IgD–/CD27+ class-switched memory B cells (3.8% vs. 8.7%, P=0.05) than HC. No difference between GPA and MPA patients vs. HC was noted for the expression of the activation markers (CD86 and CD95) or for the inhibitory receptors (CD22, CD32, CD72 and FCRL5) within B cells. Percentage of B-cell expressing CD69 was significantly higher in GPA (3.0% vs. 1.5%, P=0.02) and MPA (5.2% vs. 1.5%, P=0.019) compared to HC, respectively, as well as CD40 expression in GPA compared to HC (MFI ratio 20.57 vs 48.59, P=0.038). Expression of BAFF-R was strikingly lower in GPA and MPA compared to HC (MFI ratio 11.5 vs. 45.2, P<0.001 for GPA, and 14.0 vs. 45.2, P=0.003 for MPA). Finally, we found significantly more IL-6-producing B cells in GPA than in HC (25.7% vs. 14.9%, P<0.001), whereas IL-6-producing B cells were decreased in MPA compared to HC (4.6% vs. 14.9%, P=0.0049). In contrast, the frequency of TNFα-producing B cells were lower in GPA and MPA patients than in HC (15.9% and 8.4% vs. 30.0%, P=0.008 and P=0.006, respectively). T cell analyses found more Th2 (1.76% vs. 1.0%, P=0.028), Th9 (1.0% vs. 0.2%, P<0.001) and Th17 (1.44% vs 0.90%, P=0.03) cells in GPA compared to HC, whereas no difference was noted between MPA and HC. The percentage of Tregs was similar between GPA and MPA vs. HC. However, the FoxP3low/CD25+ T cell subset, that includes both naive Tregs and non-regulatory effector T cells, was significantly higher in GPA (6.4% vs. 4.1%, P=0.016) than in HC. No difference between groups was noted regarding the proportion of follicular helper T cells.
Conclusion: Main phenotypic characteristics of lymphocytes in GPA and MPA patients are an increased expression CD69 and CD40 activation markers and decreased expression of BAFF-R on B cells, suggesting a role of this cytokine. In addition, IL-6-producing B cells were increased in GPA whereas TNF-α-producing B cells were decreased, raising the question of the potential benefit of anti-IL-6. GPA patients differed from MPA patient by a skewed distribution of Th2, Th9 and Th17 cells.
To cite this abstract in AMA style:London J, Dumoitier N, Dion J, Chaigne B, Lofek S, Cohen P, Le Jeunne C, Varin-Blank N, Guillevin L, Terrier B, Mouthon L. Phenotypic and Functional Perturbations of Peripheral B and T Lymphocytes in Granulomatosis with Polyangiitis and Microscopic Polyangiitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/phenotypic-and-functional-perturbations-of-peripheral-b-and-t-lymphocytes-in-granulomatosis-with-polyangiitis-and-microscopic-polyangiitis/. Accessed July 11, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/phenotypic-and-functional-perturbations-of-peripheral-b-and-t-lymphocytes-in-granulomatosis-with-polyangiitis-and-microscopic-polyangiitis/