title: B-cell numbers and phenotype at clinical relapse following rituximab therapy differ in SLE patients according to anti-dsDNA antibody levels.
abstract: OBJECTIVE
  To correlate the kinetics of B-cell repopulation with relapse after B-cell depletion therapy in SLE patients and address whether variation in relapse rate, B-cell numbers and phenotype are related to anti-dsDNA antibody levels.
  
  
  METHODS
  Sixty-one patients with refractory SLE were treated with a standard rituximab regimen. Clinical and serological measures of disease activity and B-cell numbers were assessed. B-cell phenotype was examined in a subgroup of patients by flow cytometry.
  
  
  RESULTS
  Disease relapse was substantially delayed beyond B-cell repopulation, and early relapse was associated with a faster rate of repopulation. At relapse, B-cell numbers were significantly lower than at baseline in patients with high anti-dsDNA antibody levels (> 100  IU/ml) but not in patients with low anti-dsDNA antibody levels. Of the patients with high anti-dsDNA antibodies at baseline, levels fell significantly only in those patients who remained in remission after repopulation. Relapse with high anti-dsDNA antibody levels was associated with an increased percentage of IgD(-)CD27(hi) plasmablasts, whereas relapse with low anti-dsDNA antibody levels was accompanied by an increased percentage of IgD(-)CD27(-) B cells.
  
  
  CONCLUSIONS
  Anti-dsDNA antibody levels distinguished two patient groups, which differ in their B-cell number and phenotype at relapse following rituximab, and suggest that different B-cell pathologies exist in SLE. The data imply that B-cell numbers should be kept very low for a sustained period in patients with high dsDNA binding, therefore justifying a more aggressive regimen.
authors.affiliation: Centre for Rheumatology, University College London, 5 University Street, London WC1E 6JF, UK.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Lazarus
authors.forename: Tabitha
authors.initials: T
authors.lastname: Turner-Stokes
authors.forename: Konstantia-Maria
authors.initials: KM
authors.lastname: Chavele
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ehrenstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000276:immunology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018951:Antigens, CD20; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002648:Child; D010450:Endopeptidases / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007155:Immunologic Factors; D000069283:Rituximab; D010450:Endopeptidases; C098502:double-stranded DNA-stimulated protease