tailieunhanh - Báo cáo y học: " Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. | Daridon et al. Arthritis Research Therapy 2010 12 R204 http content 12 6 R204 RESEARCH ARTICLE Open Access Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus z- P s I f 1 f 1 1 3 Capucine Daridon Daniela Blassfeld Karin Reiter Henrik E Mei Claudia Giesecke David M Goldenberg Arne Hansen1 Arwed Hostmann1 Daniela Frolich1 Thomas Dorner1 2 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 cD27negatlve 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 b7 integrin and b1 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 b7 integrin while the expression