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

Abstract

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.

• Authors: A M Jacobi, D M Goldenberg, F Hiepe, A Radbruch, G R Burmester, T Dörner
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 67 Issue 4 Pg. 450-7 (Apr 2008) ISSN: 1468-2060 [Electronic] England
• PMID: 17673490 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• CD22 protein, human
• Sialic Acid Binding Ig-like Lectin 2
• Tumor Necrosis Factor Receptor Superfamily, Member 7
• epratuzumab

Topics

• Adult
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Humanized
• B-Lymphocyte Subsets (drug effects, immunology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Female
• Humans
• Lupus Erythematosus, Systemic (immunology)
• Lymphocyte Activation (drug effects)
• Male
• Sialic Acid Binding Ig-like Lectin 2 (blood)
• Tumor Necrosis Factor Receptor Superfamily, Member 7 (blood)