B-cell numbers and phenotype at clinical relapse following rituximab therapy differ in SLE patients according to anti-dsDNA antibody levels

• Published in: Rheumatology (Oxford, England) Vol. 51; no. 7; pp. 1208 - 1215
• Main Authors: Lazarus, Mark N., Turner-Stokes, Tabitha, Chavele, Konstantia-Maria, Isenberg, David A., Ehrenstein, Michael R.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2012
• Subjects: 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; Biological and medical sciences; Child; Clinical Science; Diseases of the osteoarticular system; Endopeptidases - blood; Endopeptidases - immunology; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Immunity, Cellular; Immunologic Factors - therapeutic use; Immunomodulators; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Phenotype; Rituximab; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Treatment Outcome; Young Adult; Antineoplastic agent; Human; Immunopathology; Connective tissue disease; Skin disease; Relapse; Antibody; CD20 antibody; Rheumatology; Rituximab; Autoimmune disease; B-Lymphocyte; anti-DNA antibodies; Immunomodulator; Phenotype; Systemic lupus erythematosus; Treatment; DNA; Systemic disease; β Cell; Immunosuppressive agent
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/ker526

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. 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. 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. 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.