Virus and Autoimmune Diseases: EBV is a Possibile Cause of Rheumatoid Arthritis
Journal of Nihon University Medical Association
ウイルスと自己免疫疾患―原因としての Epstein-Barr ウイルスの可能性
Some viruses can accelerate the development of autoimmune diseases in certain individuals. In this issue, we discuss the hypothesis that certain viruses impair immune tolerance. As one example, we discuss the relationship between rheumatoid arthritis (RA) and Epstein-Barr virus (EBV). EBV is well known to be associated with African Burkitt's B cell lymphoma, nasopharyngeal carcinoma and infectious mononucleosis. EBV has also been implicated in the pathogenesis of RA, based on indirect evidence,
... such as the presence of EBV particles in affected joint tissues, antigenic cross reactions between EBV and human proteins, and elevated humoral and cellular anti-EBV immune responses in patients. Since EBV plays an important role in polyclonal B cell activation, this virus might be associated with autoimmune dysfunction in patients with RA. We cloned the SAP/SH2D1A (signaling lymphocytic-activation molecule associated protein/Src homology 2 domain-containing protein) gene from peripheral leukocytes of patients with IgA nephropathy. SAP is essential for late B cell responsiveness, the development of long-term humoral immunity and the induction of cytotoxic T cells against EBV; it may also be involved in the regulation of the pathogenesis of RA. In the patients, expression of the SAP gene was decreased in the peripheral T cells that are thought to play critical roles, in conjunction with cytotoxic T cells and natural killer cells, in the elimination of EBV-infected B cells. Humanized mice (NOD/Shi-scid/IL-2Rã null (NOG) mice transplanted with CD34 + hematopoietic stem cells) were inoculated with EBV and examined pathologically for signs of arthritis; erosive arthritis accompanied by synovial membrane proliferation, pannus formation and bone marrow edema were observed. These findings strongly suggest a causative role of EBV in RA.