CD21−/low Marginal Zone B Cells Highly Express Fc Receptor–like 5 Protein and Are Killed by Anti–Fc Receptor–like 5 Immunotoxins in Hepatitis C Virus–Associated Mixed Cryoglobulinemia Vasculitis. Issue 2 (February 2014)

• Record Type: Journal Article
• Authors: Terrier, Benjamin; Nagata, Satoshi; Ise, Tomoko; Rosenzwajg, Michelle; Pastan, Ira; Klatzmann, David; Saadoun, David; Cacoub, Patrice
• Is Part Of: Arthritis & rheumatology. Volume 66:Issue 2(2014)
• Page Start: 433
• Page End: 443
• Publication Date: 2014-02
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38222
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38222-sec-0001" sec-type="section"> <title>Objective</title> <p>Hepatitis C virus (HCV) is associated with B cell lymphoproliferative disorders, including mixed cryoglobulinemia (MC) vasculitis and B cell non‐Hodgkin's lymphoma. The expansion of clonal and autoreactive rheumatoid factor–bearing CD21<sup>−/low</sup> marginal zone (MZ) B cells was demonstrated in patients with HCV‐associated MC vasculitis. Fc receptor–like (FCRL) proteins comprise a family of immunoregulatory proteins preferentially expressed on B lineage cells. The goal of this study was to investigate the expression of FCRL proteins 1–5 on B cells from patients with HCV‐associated MC vasculitis.</p> </sec> <sec id="art38222-sec-0002" sec-type="section"> <title>Methods</title> <p>Expression of FCRL proteins 1–5 was assessed by flow cytometry on B cells from 15 HCV‐infected patients with type II MC (7 of whom had B cell non‐Hodgkin's lymphoma), 20 HCV‐infected patients without MC, and 20 healthy donors. To evaluate FCRL‐5 as an immunotherapy target in HCV‐associated MC vasculitis, 2 anti–FCRL‐5 recombinant immunotoxins were produced using anti–FCRL‐5 monoclonal antibodies and <italic>Pseudomonas</italic> exotoxin.</p> </sec> <sec id="art38222-sec-0003" sec-type="section"> <title>Results</title> <p>Expression of FCRLs 2, 3, and 5 was markedly increased while expression of FCRL‐1 was decreased on clonal CD21<sup>−/low</sup> MZ B cells, as compared with other B cell subsets, from HCV‐infected patients and healthy donors. However, there was no difference in the pattern of FCRL expression between HCV‐MC patients with lymphoma and those without lymphoma. The anti–FCRL‐5 immunotoxins showed specific cytotoxicity against FCRL‐5–expressing clonal CD21<sup>−/low</sup> MZ B cells isolated from HCV‐infected patients as well as FCRL‐5–transfected cell lines. No cytotoxicity against T cells or conventional B cells was observed.</p> </sec> <sec id="art38222-sec-0004" sec-type="section"> <title>Conclusion</title> <p>These findings suggest that FCRL‐5–targeting therapies could be a specific treatment for HCV‐associated MC vasculitis and other FCRL‐5–positive autoimmune B cell disorders.</p> </sec> </abstract>