Potential role of Epstein-Barr virus in Sjögren's syndrome and rheumatoid arthritis.

In the pathogenesis of Sjögren's syndrome (SS), a role for Epstein-Barr virus (EBV) has been suggested because; (a) EBV is present in salivary gland epithelial cells of healthy individuals, and exaggerated immune responses against EBV could play a role in the destruction of salivary glands in SS; (b) SS salivary gland biopsies contain increased levels of EBV DNA compared to normal salivary glands, indicating viral reactivation and inability of lymphoid infiltrates to control EBV replication in patients with SS; and (c) salivary gland epithelial cells in patients with SS express high levels of HLA-DR antigens and may present EBV associated antigens to immune T cells in patients with SS. Therefore, SS may represent a situation where genetically predisposed individuals (i.e., HLA-DR3-DQA4-DQB2) have a persistent but ineffectual T cell immune response against EBV at its site of latency. In the case of rheumatoid arthritis (RA), evidence for a potential role of EBV includes the following: (a) EBV encoded proteins share antigenic and sequence similarity to proteins found in the synovial tissues. These crossreactive proteins include EBV protein gp110 (BALF-4) and the beta chain of HLA-DR4. Also, the human and mycobacterial 65 kDa heat shock proteins have a sequence similar to that of EBV encoded proteins; (b) patients with RA have increased frequency and levels of antibodies against specific epitopes on EBV encoded EBNA-1 (BKRF-1) and EBNA-3 (BERF-1) antigens; and (c) lymphocytes from patients with RA have decreased ability to limit outgrowth of autologous EBV infected lymphocytes, probably due to defects in release of interferon gamma.