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Publication Detail
B-cell numbers and phenotype at clinical relapse following rituximab therapy differ in SLE patients according to anti-dsDNA antibody levels.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Comparative Study
  • Authors:
    Lazarus MN, Turner-Stokes T, Chavele K-M, Isenberg DA, Ehrenstein MR
  • Publication date:
    07/2012
  • Pagination:
    1208, 1215
  • Journal:
    Rheumatology (Oxford)
  • Volume:
    51
  • Issue:
    7
  • Status:
    Published
  • Country:
    England
  • PII:
    ker526
  • Language:
    eng
  • Keywords:
    Adolescent, Adult, Aged, Antibodies, Antinuclear, Antibodies, Monoclonal, Murine-Derived, Antigens, CD20, B-Lymphocytes, Child, Endopeptidases, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Immunity, Cellular, Immunologic Factors, Lupus Erythematosus, Systemic, Male, Middle Aged, Phenotype, Rituximab, Treatment Outcome, Young Adult
Abstract
OBJECTIVES: 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‚ÄČ 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. CONCLUSION: 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.
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