title: Decreased CD5⁺ B cells in active ANCA vasculitis and relapse after rituximab.
abstract: OBJECTIVE
  B cell significance in ANCA disease pathogenesis is underscored by the finding that ANCA alone can cause disease in mouse models and by the effectiveness of rituximab as therapy in ANCA-small vessel vasculitis (ANCA-SVV). To avoid infections and adverse events from therapy, clinicians require improved markers of disease activity and impending relapse to guide immunosuppression strategies after rituximab treatment.
  
  
  METHODS
  The B cell phenotype was investigated in patients with active ANCA-SVV and in remission. From 2003 to 2009, 54 patients were followed longitudinally for 4-99 months and compared with 68 healthy controls. In a subset of 19 patients, the B cell immunophenotype was examined in samples after rituximab therapy.
  
  
  RESULTS
  Patients with active ANCA-SVV had lower %CD5(+) B cells, whereas %CD5(+) B cells from patients in remission were indistinguishable from healthy controls. After rituximab, median time to relapse was 31 months in patients maintaining normalized %CD5(+) B cells, with or without maintenance immunosuppression. Among patients whose B cells repopulated with low %CD5(+) B cells or had a sharply declining %CD5(+) B cells, those who were on low or no maintenance immunosuppression relapsed sooner (median 17 months) than patients who were maintained on high levels of oral maintenance immunosuppression (29 months; P=0.002).
  
  
  CONCLUSIONS
  The %CD5(+) B cells, as a component of the human B regulatory cell phenotype, is a useful indicator of disease activity, remission, and future relapse, and thus may guide remission maintenance therapy after rituximab treatment.
authors.affiliation: UNC Kidney Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA. donna_bunch@med.unc.edu
authors.forename: Donna O'Dell
authors.initials: DO
authors.lastname: Bunch
authors.forename: JulieAnne G
authors.initials: JG
authors.lastname: McGregor
authors.forename: Nirmal B
authors.initials: NB
authors.lastname: Khandoobhai
authors.forename: Lydia T
authors.initials: LT
authors.lastname: Aybar
authors.forename: Madelyn E
authors.initials: ME
authors.lastname: Burkart
authors.forename: Yichun
authors.initials: Y
authors.lastname: Hu
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hogan
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Poulton
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Berg
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Falk
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Nachman
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018956:CD5 Antigens / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D018956:CD5 Antigens; D007166:Immunosuppressive Agents; D000069283:Rituximab