Epstein-Barr-Virus-Infected CD15 (Lewis X)-Positive Hodgkin-Lymphoma-Like B Cells in Patients with Rheumatoid Arthritis

Hirotake Inomata§, 1, Masami Takei*, §, 1, Hiroyuki Nakamura2, Shigeyoshi Fujiwara2, Hidetaka Shiraiwa1, Noboru Kitamura1, Shunsei Hirohata3, Hiroyuki Masuda1, 4, Jin Takeuchi1, Shigemasa Sawada*, 1
1 Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
2 Department of Infectious Diseases, National Research Institute for Child Health and Development, Tokyo, Japan
3 Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan
4 Intellim Corporation, Tokyo, Japan

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© Inomata et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to these authors at the Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Itabashi-ku, Tokyo, Japan; Tel: +81-3-3972-8111; Fax: +81-3-3972-2893; E-mails:,
§ These authors contributed equally to this work


Patients with rheumatoid arthritis (RA), especially those who are treated with methotrexate (MTX), might have an increased risk of Hodgkin lymphoma (HL), a malignancy that is associated with Epstein-Barr virus (EBV). Here we describe a monoclonal EBV-infected B-lymphoblastoid cell line (LCL) called TKS-1 that was established from cells that spontaneously converted from an MTX-treated RA patient. TKS-1 has properties similar to HL cells and it is distinctly different from control LCLs established from normal individuals. TKS-1 cells express the HL -associated surface markers CD15 and CD30 (Takei et al. 1989). Like Hodgkin Reed-Sternberg (H-RS) cells of EBV-positive HL, TKS-1 cells express EBNA1 mRNA transcribed from the Qp promoter of the virus, whereas control LCLs use the Cp or Wp promoter to transcribe mRNA. TKS-1 cells can proliferate in an anchorage-independent manner and possess a cloning efficiency comparable to that of the Burkitt lymphoma (BL) line Raji. In addition, two EBV-positive LCLs established by cocultivated CD34+ cells isolated from the bone marrow of patients with RA and peripheral blood B lymphocytes from a healthy EBV-seronegative individual also expressed CD15. These results indicate that EBV-infected B-lymphoblastoid cells from patients with RA tend to acquire properties similar to HL cells.