Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls

• Published in: Annals of the rheumatic diseases Vol. 67; no. 4; pp. 450 - 457
• Main Authors: Jacobi, A M, Goldenberg, D M, Hiepe, F, Radbruch, A, Burmester, G R, Dörner, T
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.04.2008; BMJ; Elsevier Limited
• Subjects: Adult; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; B-Lymphocyte Subsets - drug effects; B-Lymphocyte Subsets - immunology; Biological and medical sciences; Cell growth; Cell Proliferation - drug effects; Cells, Cultured; Diseases of the osteoarticular system; Female; Humans; Immunomodulators; Lupus; Lupus Erythematosus, Systemic - immunology; Lymphocyte Activation - drug effects; Lymphocyte receptors; Lymphoma; Male; Medical sciences; Pharmacology. Drug treatments; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sialic Acid Binding Ig-like Lectin 2 - blood; Tumor Necrosis Factor Receptor Superfamily, Member 7 - blood; Epratuzumab; Human; Immunopathology; Connective tissue disease; Skin disease; Rheumatology; Autoimmune disease; B-Lymphocyte; Monoclonal antibody; Immunomodulator; Blood cell; Systemic lupus erythematosus; Systemic disease; β Cell; Comparative study
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/ard.2007.075762

Objective:B lymphocytes have been implicated in the pathogenesis of lupus and other autoimmune diseases, resulting in the introduction of B cell-directed therapies. Epratuzumab, a humanised anti-CD22 monoclonal antibody, is currently in clinical trials, although its effects on patients’ B cells are not completely understood.Methods:This study analysed the in vivo effect of epratuzumab on peripheral B cell subsets in 12 patients with systemic lupus erythematosus, and also addressed the in vitro effects of the drug by analysing anti-immunoglobulin-induced proliferation of isolated B cells obtained from the peripheral blood of 11 additional patients with lupus and seven normal subjects.Results:Upon treatment, a pronounced reduction of CD27– B cells and CD22 surface expression on CD27– B cells was observed, suggesting that these cells, which mainly comprise naïve and transitional B cells, are preferentially targeted by epratuzumab in vivo. The results of in vitro studies indicate additional regulatory effects of the drug by reducing the enhanced activation and proliferation of anti-immunoglobulin-stimulated lupus B cells after co-incubation with CD40L or CpG. Epratuzumab inhibited the proliferation of B cells from patients with systemic lupus erythematosus but not normal B cells under all culture conditions.Conclusions:Epratuzumab preferentially modulates the exaggerated activation and proliferation of B cells from patients with lupus in contrast to normal subjects, thus suggesting that epratuzumab might offer a new therapeutic option for patients with systemic lupus erythematosus, as enhanced B cell activation is a hallmark of this disease.