Epstein-Barr virus may increase risk of lupus

Almost everyone has been infected with Epstein-Barr virus (EBV), a member of the herpes family and one of the most common human viruses.

Symptoms of initial infection range from a typically mild childhood illness with a fever and sore throat to mononucleosis in teenagers or adults.

After the initial infection, the virus settles into the cells of the immune system called B cells, where it remains for life, mostly dormant, with occasional bouts of reactivation and replication.

Maintaining EBV infection in a latent or quiet state primarily depends on the power of another kind of immune cell, known as T cells. T cells play a major role in keeping the immune system functioning properly.

Due to its interference with immune function and promotion of certain antibodies, EBV has been implicated in systemic lupus erythematosus (SLE), commonly referred to as lupus.

Lupus is a chronic, potentially debilitating autoimmune disease that more often affects women and is also more common in African Americans. Although the specific cause of lupus is not yet known, both genetic and environmental triggers are likely to be involved.

To determine if there is an association between Epstein-Barr virus and lupus, researchers in North and South Carolina compared the prevalence of EBV antibodies in blood samples from lupus patients with those from healthy controls.

Published in the April 2005 issue of Arthritis & Rheumatism, the results of the National Institute of Environmental Health Sciences (NIEHS) study show a strong association of EBV-IgA antibodies with lupus in African Americans. In addition, their findings shed new light on variation in a T-cell response gene that might influence immune responsiveness to EBV among lupus patients.

Participants in the Carolina Lupus Study included 230 patients recently diagnosed with lupus. Ranging widely in age, the subjects were 90 percent women and 60 percent African-American. Matched for age and sex, controls were recruited from state driver's license registries. 30 percent of the enrolled controls were African-American, reflecting the racial distribution of the geographic study area. Blood samples and medical records were obtained for all participants.

Among both lupus patients and controls, African Americans had a higher prevalence of EBV-IgG antibodies – the telltale sign of having a history of EBV infection – than white subjects. However, another antibody, EBV-IgA, seen with repeat or reactivated EBV infection, was also more common in African Americans with lupus. EBV-IgA was found in 66 percent of African-American patients, and calculated at increasing the odds for lupus by 5 to 6 fold. Among white lupus patients, the EBV-IgA association was modest, yet increased significantly with age. The association also appeared stronger in older African Americans than younger patients.

Among lupus patients, both African-American and white, researchers also observed a genetic variation in CTLA-4, a protein that works on T cells in regulating immunity, and which significantly increased the risk of lupus associated with EBV-IgA antibodies. This variation was previously linked to risk of lupus in younger African Americans in the Carolina Lupus Study.

"The racial difference in the association between EBV-IgA and SLE is intriguing, especially since African Americans have a higher risk of SLE, tend to develop the disease earlier, and often have a more severe course of disease," notes the study's leading author, Christine G. Parks, Ph.D., who performed the study as a post-doctoral fellow at the NIEHS, one of the National Institutes of Health, in Research Triangle Park, North Carolina. Dr. Parks is presently employed with the National Institute for Occupational Safety and Health Sciences in Morgantown, West Virginia. "One explanation could be that there are more opportunities for reinfection among African Americans, given the higher population prevalence of infection and likelihood of encountering and becoming infected with new viral strains. Alternatively, other factors independently related to the immune response to EBV and loss of latency could vary by race, with the same difference being related to the differential risk of SLE."

Providing solid new serum-based evidence on the link between lupus and Epstein-Barr virus, this study also calls attention to the need for continued research into the role of race, age, and genetic variation in autoimmune diseases.

The National Institute of Environmental Health Sciences is a federal agency that conducts and funds basic research on the health effects of exposure to environmental agents.