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OP0194 CD21-/LO Marginal Zone-Like B Cells in HCV-Related Mixed Cryoglobulinemia Vasculitis Highly Express FCRL5 Protein and are Specifically Killed by Anti-FCRL5 Immunotoxins
  1. B. Terrier1,
  2. S. Nagata2,
  3. T. Ise2,
  4. M. Rosenzwajg3,
  5. D. Klatzmann3,
  6. D. Saadoun3,
  7. P. Cacoub3
  1. 1Cochin, Paris, France
  2. 2Cancer Biology Research Center, Sioux Falls, United States
  3. 3Pitié-Salpétrière, Paris, France

Abstract

Background Hepatitis C virus (HCV) is associated with B-cell lymphoproliferative disorders including mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. Fc receptor-like (FCRL) proteins comprise a newly identified family of immunoregulatory proteins with sequence similarity as Fc receptors. The transmembrane FCRL1-5 molecules are preferentially expressed on B lineage cells.

Objectives To analyze the expression of FCRL1-5 proteins on B cells and test the cytotoxicity of specific immunotoxins on clonal B cells.

Methods We analyzed by flow cytometry the expression of FCRL1-5 on B cells from 15 HCV-infected patients with type II MC, 20 HCV patients without MC and 20 healthy donors.

Results We found a markedly increased expression of FCRL5 and decreased expression of FCRL1 on clonal CD21-/lo marginal zone-like B cells compared to other B cell subsets from the HCV patients and healthy donors. To evaluate FCRL5 as an immunotherapy target for HCV-related lymphoproliferation, we produced two anti-FCRL5 recombinant immunotoxins (F56-IT and F25-IT) based on anti-FCRL5 monoclonal antibodies and Pseudomonas exotoxin. The immunotoxins showed specific cytotoxicity against FCRL5-expressing clonal CD21-/lo marginal zone-like B cells isolated from HCV patients as well as FCRL5-transfected cell lines. In contrast, no cytotoxicity was observed against T cells or conventional B cells.

Conclusions Taken together, our findings suggest that FCRL5-targeting therapies could be a specific treatment of HCV-related lymphoproliferation and other FCRL5-positive malignancies and/or autoimmune B-cell disorders.

Disclosure of Interest None Declared

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