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Abstract: FR-PO824

Minimal Residual Autoimmunity After Rituximab in ANCA-Associated Vasculitis Patients

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • van Dam, Laura Sophie, LUMC, Leiden, Netherlands
  • Oskam, Jelle Matthias, LUMC, Leiden, Netherlands
  • Kamerling, Sylvia, LUMC, Leiden, Netherlands
  • Arends, Eline Jana, LUMC, Leiden, Netherlands
  • Bredewold, Edwin, LUMC, Leiden, Netherlands
  • Van dongen, Jacques J.j.m., LUMC, Leiden, Netherlands
  • Rabelink, Ton J., LUMC, Leiden, Netherlands
  • van Kooten, Cees, LUMC, Leiden, Netherlands
  • Teng, Yoe Kie Onno, LUMC, Leiden, Netherlands

Group or Team Name

  • Lupus, Vasculitis and Complement Center of Expertise (LUVACS) LUMC Leiden
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

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

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

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.