Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Background: B-cell depletion with rituximab (RTX) is an effective treatment for ANCA-associated vasculitis (AAV) patients. Repeated RTX upon B-cell repopulation or return of ANCAs improved therapeutic efficacy, which indicates the presence of minimal residual autoimmunity (MRA) after RTX. Therefore, this study aimed to perform in-depth phenotypic and functional analyses of B and plasma cells after RTX in AAV.
Methods: Methods: EuroFlow-based highly sensitive flow cytometry (HSFC) was used during longitudinal follow-up of RTX-treated AAV patients (n=12). To investigate MRA in the memory B-cell compartment after RTX, peripheral blood mononuclear cells (PBMCs) were stimulated with CpG, IL-2 and IL-21 in vitro to induce plasma cells (PCs) and ANCA-IgG and -IgM were measured in these supernatants and in paired serum samples by ELISA.
Results: Results: By employing HSFC we demonstrated that 12 weeks after RTX, low but significant numbers of circulating CD19+ B cells (0.21*106 cells/L) could still be detected (reduction of -99.7%). While naïve B-cells, memory B-cells and CD20+ plasmablasts (PB) were rapidly depleted, CD20– PCs were reduced slower and depleted incompletely. Residual CD20– PCs were 0.05*106 cells/L (-95.8% from baseline), whereof 57% were mature CD138+ PCs. Early repopulation at 12 weeks was dominated by CD20–CD138– PCs, followed by CD20+ PBs at 24 weeks while memory and naïve B cells remained suppressed. Simultaneously, serum ANCA IgG, IgM and IgA, produced by autoreactive PCs, decreased but did not disappear after RTX. Interestingly, 24 weeks after RTX, serum anti-MPO IgM increased in 3/4 patients, which associated with repopulating CD20+ PBs. This suggested remaining autoreactive B cells despite RTX treatment, which was further studied by in vitro PBMC cultures. In these supernatants both anti-MPO-IgG and -IgM were detected at baseline, whereas anti-MPO IgG disappeared after RTX, in contrast to anti-MPO IgM, which was detected 24 weeks after RTX.
Conclusion: Conclusion: RTX results in a strong but not complete B cell depletion. In-depth analysis demonstrated that both ANCA-producing PCs and ANCA-memory B cells can be detected after RTX, indicating residual B-cell autoimmunity in AAV patients. Further identification of MRA could be worthwhile for guiding personalized treatment in AAV patients.
To cite this abstract in AMA style:van Dam L, Oskam J, Kamerling S, Arends E, Bredewold E, Berkowska M, van Dongen J, Rabelink T, van Kooten C, Teng O. Minimal Residual Autoimmunity After Rituximab in ANCA-associated Vasculitis Patients [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/minimal-residual-autoimmunity-after-rituximab-in-anca-associated-vasculitis-patients/. Accessed April 13, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/minimal-residual-autoimmunity-after-rituximab-in-anca-associated-vasculitis-patients/