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Gleaning relapse risk from B cell phenotype: decreased CD5+ B cells portend a shorter time to relapse after B cell depletion in patients with ANCA-associated vasculitis
  1. Donna O Bunch1,
  2. Carmen E Mendoza1,
  3. Lydia T Aybar1,
  4. Elizabeth S Kotzen1,
  5. Kerry R Colby1,
  6. Yichun Hu1,
  7. Susan L Hogan1,
  8. Caroline J Poulton1,
  9. John L Schmitz2,
  10. Ronald J Falk1,
  11. Patrick H Nachman1,
  12. William F Pendergraft1,
  13. JulieAnne G McGregor1
  1. 1Department of Medicine, University of North Carolina (UNC) Kidney Center, Chapel Hill, North Carolina, USA
  2. 2Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
  1. Correspondence to Dr Donna O Bunch, Department of Medicine, UNC Kidney Center, 5005 Burnett Womack Building, Campus Box # 7155, Chapel Hill, NC 27599, USA; donna_bunch{at}med.unc.edu

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B cell depletion is an effective remission induction and maintenance therapy in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV).1–6 Rituximab targets both pathogenic effector B cells and protective regulatory B cells. To avoid infections and adverse events from therapy, clinicians require improved markers of disease activity and impending relapse to guide immunosuppression strategies following B cell depletion. We reported that CD5+ B cells, as a surrogate marker of B regulatory cells, are decreased in patients with active AAV and normalise during disease remission.7 After B cell depletion, patients who repopulated with a low or decreasing percentage of CD5+ B cells and were on low maintenance immunosuppression had a shorter time to relapse than patients on similar levels of immunosuppression with normalised CD5+ B cells or patients with similarly low CD5+ B cells but higher immunosuppression. The CD5+CD24hiCD38hi B cell subpopulation correlates inversely with active disease but parallels both interleukin (IL)-10 production and suppression of ANCA.8 CD5 may identify B cells enriched in IL-10 production, the defining cytokine of B regulatory cells.8 ,9 Whether CD5+ B cells can serve as an indicator of time to relapse without considering remission maintenance immunosuppression dose is not known. We sought to address this question and confirm our previous findings in a larger cohort by separating patients solely based on their CD5+ B cells at repopulation.

We examined B cell phenotype in 50 patients with AAV following rituximab therapy by flow cytometry (table …

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Footnotes

  • Contributors RJF, PHN, JAGM and WFP provided clinical care for the patients. JGM and ESK reviewed patients’ clinical information. DOB, LTA and JGM conceived and designed the research. Clinical flow cytometry data were provided by JLS. YH and SLH provided expert statistical analysis and interpretation. CJP obtained institutional review board approval for this study. CEM, ESK, KAC, LTA and CJP collected data. CEM, JGM, SLH, WFP and DOB interpreted the data and wrote the manuscript. All authors participated in reviewing the manuscript and approved the final version.

  • Funding This work was supported by a Program Project Grant number 5P01DK058335-14 from NIH/NIDDK and the Vasculitis Foundation.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval University of North Carolina Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement This research includes flow cytometry data derived from clinical tests and clinical information regarding disease diagnosis and disease status from 50 subjects. The final dataset includes self-reported demographic data and other clinical laboratory data. Even though the final dataset will be stripped of identifiers prior to release for sharing, we believe that there remains the possibility of deductive disclosure of subjects. Thus, we will make the data and associated documentation available to users only under a data-sharing agreement that provides for (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.

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