Possible involvement of Epstein-Barr virus in the pathogenesis of Sjogren's syndrome.

We examined the possible involvement of Epstein-Barr virus (EBV) in the pathogenesis of Sjogren's syndrome (SS) using B cell lines (BCLs) spontaneously established from the peripheral blood. These BCLs were positive for EBNA and produced a large amount of infecting EBV in culture, a feature unique to SS-BCLs. Polymerase chain reaction analysis revealed that EBV with a B95-8-like U2 region was dominant in SS-BCLs. The nucleotide sequences of the U2 region of SS-EBV obtained so far have shown high homology to those of B95-8 EBV. However, there was a substantial amount of deletion and substitution of nucleotides within the U2 region of SS-EBV when compared with B95-8 EBV. This might enable SS-BCLs to escape immune recognition by cytotoxic T cells specific to EBNA-2. In addition, SS-EBV contains the sequence that spans the B95-8-deleted region. Furthermore, transfer of SS-BCLs to SCID mice induced monoclonal lymphoproliferative disorders that resembled those arising in SS. These data further support the motion that reactivation of EBV is deeply involved in polyclonal B cell activation and the development of B cell malignancies in SS.