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.(ABSTRACT TRUNCATED AT 250 WORDS)
Fox
R I
RI
Department of Rheumatology and Immunology, Scripps Clinic and Research Foundation, La Jolla, CA.
Luppi
M
M
Pisa
P
P
Kang
H I
HI
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000382:microbiology*; D001853:Bone Marrow / Q000382:microbiology; D004279:DNA, Viral / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D012469:Salivary Glands / Q000382:microbiology; D012859:Sjogren's Syndrome / Q000382:microbiology*; D013583:Synovial Membrane / Q000473:pathology; D014412:Tumor Virus Infections / Q000150:complications / Q000382:microbiology; D014775:Virus Activation
D004279:DNA, Viral