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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 6/2010

Open Access 01-12-2010 | Research article

Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus

Authors: Capucine Daridon, Daniela Blassfeld, Karin Reiter, Henrik E Mei, Claudia Giesecke, David M Goldenberg, Arne Hansen, Arwed Hostmann, Daniela Frölich, Thomas Dörner

Published in: Arthritis Research & Therapy | Issue 6/2010

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Abstract

Introduction

Epratuzumab, a humanized anti-CD22 monoclonal antibody, is under investigation as a therapeutic antibody in non-Hodgkin's lymphoma and systemic lupus erythematosus (SLE), but its mechanism of action on B-cells remains elusive. Treatment of SLE patients with epratuzumab leads to a reduction of circulating CD27negative B-cells, although epratuzumab is weakly cytotoxic to B-cells in vitro. Therefore, potential effects of epratuzumab on adhesion molecule expression and the migration of B-cells have been evaluated.

Methods

Epratuzumab binding specificity and the surface expression of adhesion molecules (CD62L, β7 integrin and β1 integrin) after culture with epratuzumab was studied on B-cell subsets of SLE patients by flow cytometry. In addition, in vitro transwell migration assays were performed to analyze the effects of epratuzumab on migration towards different chemokines such as CXCL12, CXCL13 or to CXCR3 ligands, and to assess the functional consequences of altered adhesion molecule expression.

Results

Epratuzumab binding was considerably higher on B-cells relative to other cell types assessed. No binding of epratuzumab was observed on T-cells, while weak non-specific binding of epratuzumab on monocytes was noted. On B-cells, binding of epratuzumab was particularly enhanced on CD27negative B-cells compared to CD27positive B-cells, primarily related to a higher expression of CD22 on CD27negative B-cells. Moreover, epratuzumab binding led to a decrease in the cell surface expression of CD62L and β7 integrin, while the expression of β1 integrin was enhanced. The effects on the pattern of adhesion molecule expression observed with epratuzumab were principally confined to a fraction of the CD27negative B-cell subpopulation and were associated with enhanced spontaneous migration of B-cells. Furthermore, epratuzumab also enhanced the migration of CD27negative B-cells towards the chemokine CXCL12.

Conclusions

The current data suggest that epratuzumab has effects on the expression of the adhesion molecules CD62L, β7 integrin and β1 integrin as well as on migration towards CXCL12, primarily of CD27negative B-cells. Therefore, induced changes in migration appear to be part of the mechanism of action of epratuzumab and are consistent with the observation that CD27negative B-cells were found to be preferentially reduced in the peripheral blood under treatment.
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Metadata
Title
Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus
Authors
Capucine Daridon
Daniela Blassfeld
Karin Reiter
Henrik E Mei
Claudia Giesecke
David M Goldenberg
Arne Hansen
Arwed Hostmann
Daniela Frölich
Thomas Dörner
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 6/2010
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3179

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