New-onset ANCA-associated Vasculitis Is Associated with Significant Phenotypic B Cell Dysfunction

Emilie Chan¹, Susan Hartzell ², Lisa Anderson ², Chiara Cantarelli ², Chiara Guglielmo ², Ioannis Tassiulas ³, Sofia Andrighetto ², Andrea Angeletti ⁴, Joaquin Manrique Escola ⁵ and Paolo Cravedi ², ¹Mount Sinai Hospital, New York, NY, ²Mount Sinai Hospital, New York, ³Icahn School of Medicine, New York, ⁴Sant'Orsola-Malpighi Hospital, Bologna, Italy, ⁵Complejo Hospital de Navarra, Pamplona, Spain

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ANCA, B cells, flow cytometry and glomerulonephritis, Vasculitis

Session Information

Date: Monday, November 11, 2019

Title: B Cell Biology & Targets In Autoimmune & Inflammatory Disease Poster

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: ANCA-associated vasculitis (AAV) is characterized by the production of auto-antibodies and can be treated with rituximab, a B cell-depleting agent. Despite this, limited data are available characterizing the B cell dysfunction associated with AAV.

Methods: We performed comprehensive flow-cytometric analyses of major cell markers of B cell function in 20 patients with new diagnosis of AAV with renal involvement and 10 healthy controls (HC). Peripheral blood samples were taken at clinical onset prior to treatment initiation for AAV patients. We measured CD25^hi CD71^hi B regulatory cells; subpopulations of memory B cells, including IgD⁺CD27^– naive, IgD⁺CD27⁺unswitched, IgD^–CD27⁺ switched, and IgD^–CD27^– double negative; and CD38^hiCD27^hi plasma cells and their expression of CD138.

Results: We found significantly increased percentages of of CD3^–CD56^–CD19⁺ B cells in AAV patients compared to HC (Fig. 1A). We did not find a significant difference in CD25^hi CD71^hi B regulatory cells between AAV and HC (Fig. 1B). AAV patients had increased frequency of double negative IgD^–CD27^– memory B cells but no difference in the naïve, switched, or unswitched memory B cell subpopulations (Fig. 1C-F). We found significantly higher levels of CD38^hiCD27^hi plasma cells in AAV patients, with greater CD138^– but no difference in CD138⁺ expression between groups (Fig. G-I).

Conclusion: Patients with new diagnosis AAV display a unique phenotype of B cell dysfunction that is characterized by an increase in the double negative (DN) memory B cell population, which has been implicated in other autoimmune diseases, and an increase in plasma cells, suggesting persistent antibody production. We did not demonstrate a difference in B regulatory cells, a departure from previously published results that may be explained by our study of early disease activity.

B cell abstract

Fig. 1. Percentages of CD3-CD56-CD19+ B cells -A- and CD25 hi CD71hi B regulatory cells -B- in ANCA-associated vasculitis patients -AAV, n=20- and healthy controls -HC, n=10-. Percentages of B memory cell subpopulations: IgD+CD27- naive, IgD+CD27+ unswitched, IgD-CD27+ switched, and IgD-CD27- double negative -C-F-. Percentages of CD38hiCD27hi plasma cells with expression of CD138- and CD138+ -G-I-. *p<0.05.

Disclosure: E. Chan, None; S. Hartzell, None; L. Anderson, None; C. Cantarelli, None; C. Guglielmo, None; I. Tassiulas, None; S. Andrighetto, None; A. Angeletti, None; J. Manrique Escola, None; P. Cravedi, None.

To cite this abstract in AMA style:

Chan E, Hartzell S, Anderson L, Cantarelli C, Guglielmo C, Tassiulas I, Andrighetto S, Angeletti A, Manrique Escola J, Cravedi P. New-onset ANCA-associated Vasculitis Is Associated with Significant Phenotypic B Cell Dysfunction [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/new-onset-anca-associated-vasculitis-is-associated-with-significant-phenotypic-b-cell-dysfunction/. Accessed .

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