Contact: Heather Woolwine
843.792.7669
April 12, 2005
CHARLESTON - An MUSC study suggests a common viral infection
may increase risk of lupus in African Americans. Findings also show that a genetic
variation may affect the immune response to Epstein-Barr virus in lupus patients.
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 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
B cells in the immune system, where it remains for life, mostly dormant, with
occasional bouts of reactivation and replication.
Due to its interference with immune function and promotion of certain antibodies,
EBV was implicated in systemic lupus erythematosus (SLE), 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 involved.
“Although EBV was a known risk factor for lupus for more than three decades,
this is the first study to show that an interaction between a gene of the immune
system (CTLA-4) and environment (EBV) increases the risk by several folds,”
said Janardan Pandey, Ph.D., MUSC professor of Microbiology and Immunology.
“In other words, there are inter-individual differences in susceptibility
to EBV associated lupus. In addition to the Carolina Lupus Study, we have shown
the involvement of CTLA-4 in patients from Korea. Thus, this gene appears to
be an important risk factor for lupus in diverse racial groups. It is important
however, not to focus too much on any one gene. Like most human diseases, lupus
is the result of interactions among many genes as well as environmental factors.”
Published in the April 2005 issue of Arthritis & Rheumatism
(http://www.interscience.wiley.com/journal/arthritis), the results of the
study show a strong association of EBV-IgA antibodies with lupus in African
Americans. In addition, the findings shed new light on variation in a T-cell
response gene that might influence immune responsiveness to EBV among lupus
patients. Maintaining EBV infection in a latent or quiet state primarily depends
on the power of T cells, which play a major role in keeping the
immune system functioning properly.
Among both lupus patients and controls, African Americans had a higher
prevalence of EBV-IgG antibodies than white subjects, the telltale sign of a
history of EBV infection. 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," said Christine G. Parks, Ph.D., NIEHS, one of the National Institutes of Health in Research Triangle Park, North Carolina. "One explanation could be that there are more opportunities for re-infection 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."
#####