Epstein-Barr virus and human autoimmune diseases: possibilities and pitfalls

Epidemiologic studies suggest that human autoimmune disease involves both genetic and environmental components. Although a great deal has been learned about genetic components (i.e. histocompatibility antigens), little is known about the environmental factors. Because of its ubiquitous nature and ability to stimulate lymphoid responses, Epstein-Barr virus (EBV) has been examined as a potential candidate, particularly in rheumatoid arthritis and systemic lupus erythematosus. No convincing evidence has been produced that it plays a primary etiologic role in these disorders. Nevertheless, EBV or a related herpesvirus may play an indirect role in perpetuating the disorder or in the development of extra-articular manifestations such as Sj?gren's syndrome (an autoimmune disorder involving the salivary glands). Current data indicates increased EBV reactivation in some patients with autoimmune diseases, as evidenced by increased viral DNA in their saliva and increased number of circulating B-cells containing EBV in their blood. These patients also have modestly elevated anti-EBV antibody titers and altered antiviral T-cell responses, as measured by the ability to prevent outgrowth of autologous EBV infected B-cells. However, the relevance of these 'abnormalities' to pathogenesis remains unknown. It is hoped that new techniques such as polymerase chain reaction will provide new insights into these questions by allowing detection of viral DNA from tissue biopsies obtained early in the course of disease and by providing a method to identify viral isolates that do not grow well in vitro.