Efforts of several research groups have been combined to identify the clinical[18-20] and molecular[21-24] FK506 clinical trial parameters that are associated with an insufficient

clinical response to RTX treatment. Our group has recently found a positive association between the presence of Epstein–Barr virus (EBV) genome in the BM of patients with RA and clinical response to RTX treatment.[25] Interestingly, RTX treatment was followed by complete clearance of EBV from the BM. The ability to respond to interferon stimulation, an essential mechanism of human anti-viral defence, may potentially predict clinical effect of RTX in patients with RA.[26, 27] Infection with EBV is one of the environmental risk factors for the development of RA.[28] The EBV glycoprotein gp110 contains a sequence identical to the motif of the HLA-DRB1 alleles within the MHC II complex; called ‘shared epitope’, it is the strongest known genetic factor for the development of RA.[29-31] Also, EBV infection in carriers of shared epitope greatly enhanced the development of RA.[30] Consequently, a compromised innate immune response towards find more EBV and poor viral clearance are attributed

to RA patients and lead to a high load of EBV-infected cells in the circulating blood and in the synovial cells, impaired cytolytic activity of T cells to EBV proteins and high titres of anti-EBV antibodies compared with healthy subjects.[32-37] B cells are currently considered critical for the primary EBV infection and for its persistence. Epstein–Barr virus activates B cells and induces their proliferation and transformation into antibody-secreting cells.[38] It has the ability to infect almost all types of B cells in vivo but naive IgM+ IgD+ B cells are the major

target in tonsils, while the latent infection is found in the memory B-cell pool.[39-41] The naive B-cell subset seems to be the cell population that shares susceptibility to RTX and EBV, so we attempted to outline phenotypic and functional changes in the peripheral blood and bone marrow B cells of patients with RA following RTX Non-specific serine/threonine protein kinase treatment and during EBV infection. Samples of BM and PB were collected from 35 patients with established RA, diagnosed according to the ACR 1987 criteria[42] before B-cell depletion therapy with anti-CD20 antibodies.[13] All patients were recruited from the Rheumatology Clinic at Sahlgrenska University Hospital, Göteborg, Sweden, during the period from January 2007 to September 2008, and all patients gave written informed consent to participate. Additionally, 18 patients with RA donated PB samples for functional analysis. Another 10 patients with RA also donated PB and synovial fluids for phenotypic B-cell analysis. All patients with RA were receiving methotrexate treatment and had not been treated with RTX previously. Clinical and demographic characteristics of the patients and their immunosuppressive treatment are presented in Table 1.