B-cell Numbers and Phenotype at Clinical Relapse Following Rituximab Therapy Differ in SLE Patients According to anti-dsDNA Antibody Levels

Rheumatology (Oxford). 2012 Jul;51(7):1208-15. doi: 10.1093/rheumatology/ker526. Epub 2012 Feb 15.

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 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Antinuclear / blood*
  • Antibodies, Antinuclear / immunology
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antigens, CD20
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Child
  • Endopeptidases / blood
  • Endopeptidases / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Cellular*
  • Immunologic Factors / therapeutic use
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Middle Aged
  • Phenotype
  • Rituximab
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Antinuclear
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Immunologic Factors
  • Rituximab
  • Endopeptidases
  • double-stranded DNA-stimulated protease