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Abstract Number: 966

Minimal Residual Autoimmunity After Rituximab in ANCA-associated Vasculitis Patients

Laura van Dam1, Jelle Oskam 2, Sylvia Kamerling 2, Eline Arends 2, Edwin Bredewold 2, Magda Berkowska 2, Jacques van Dongen 2, Ton Rabelink 2, Cees van Kooten 2 and Onno Teng 2, 1LUMC, Leiden, Zuid-Holland, Netherlands, 2LUMC, Leiden, Netherlands

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ANCA, B cell targeting and autoimmune diseases, Rituximab, Vasculitis

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Session Information

Date: Monday, November 11, 2019

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

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.


Disclosure: L. van Dam, None; J. Oskam, None; S. Kamerling, None; E. Arends, None; E. Bredewold, None; M. Berkowska, None; J. van Dongen, None; T. Rabelink, None; C. van Kooten, None; O. Teng, None.

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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