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Treatment of systemic lupus erythematosus with epratuzumab.

ABSTRACT: Systemic lupus erythematosus is a prototypic autoimmune disease characterized by abnormalities in the activity of B-cells and T-cells. A novel specific treatment for autoimmune diseases is B-cell depletion with monoclonal antibodies. Epratuzumab is a monoclonal antibody that targets CD22 antigen on B-cells. Initial phase II and two terminated early phase III studies suggest that treatment of systemic lupus erythematosus with this immunomodulatory agent is effective, well tolerated and significantly improves the patient's quality of life. In vitro studies and clinical trials with non-Hodgkin lymphoma patients indicate epratuzumab can potentially serve as a complementary drug in combination therapy with another inhibitor of B-cell activity, rituximab, which is a monoclonal anti-CD20 antibody.

SUBMITTER: Traczewski P

PROVIDER: S-EPMC3040537 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Treatment of systemic lupus erythematosus with epratuzumab.

Traczewski Pawel P Rudnicka Lidia L

British journal of clinical pharmacology 20110201 2

Systemic lupus erythematosus is a prototypic autoimmune disease characterized by abnormalities in the activity of B-cells and T-cells. A novel specific treatment for autoimmune diseases is B-cell depletion with monoclonal antibodies. Epratuzumab is a monoclonal antibody that targets CD22 antigen on B-cells. Initial phase II and two terminated early phase III studies suggest that treatment of systemic lupus erythematosus with this immunomodulatory agent is effective, well tolerated and significan ...[more]

PMID: 21219397

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Project description: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 CD27(negative) 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, ?7 integrin and ?1 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 CD27(negative) B-cells compared to CD27(positive) B-cells, primarily related to a higher expression of CD22 on CD27(negative) B-cells. Moreover, epratuzumab binding led to a decrease in the cell surface expression of CD62L and ?7 integrin, while the expression of ?1 integrin was enhanced. The effects on the pattern of adhesion molecule expression observed with epratuzumab were principally confined to a fraction of the CD27(negative) B-cell subpopulation and were associated with enhanced spontaneous migration of B-cells. Furthermore, epratuzumab also enhanced the migration of CD27(negative) B-cells towards the chemokine CXCL12. CONCLUSIONS: The current data suggest that epratuzumab has effects on the expression of the adhesion molecules CD62L, ?7 integrin and ?1 integrin as well as on migration towards CXCL12, primarily of CD27(negative) 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 CD27(negative) B-cells were found to be preferentially reduced in the peripheral blood under treatment.

Dataset Information

Treatment of systemic lupus erythematosus with epratuzumab.

Publications

Treatment of systemic lupus erythematosus with epratuzumab.

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