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

Abstract

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.