Epstein-Barr reactivation studied in patients with systemic sclerosis |…

People with systemic sclerosis (SSc) have higher levels of certain antibodies to Epstein-Barr virus, suggesting dormant viral infections are being reactivated in these patients, a new study shows.

The study, “Detection of Epstein-Barr Virus in Patients With Systemic Sclerosis: A Molecular and Serological Study“, was published in International Journal of Rheumatic Diseases.

The Epstein-Barr virus, or EBV, is best known for causing infectious mononucleosis (colloquially called “mono”). This virus can also cause non-specific flu-like illness, and most people contract EBV at some point in their lives.

After EBV infection, the virus can remain in the body’s cells in a dormant state, with the potential to reactivate later. This type of latent infection has been linked to the development of autoimmune diseases such as multiple sclerosis (MS). However, the relevance of EBV in scleroderma has not yet been fully investigated.

In this study, scientists in India analyzed blood samples from 150 people with SSc and 45 people without the disease (controls). Both groups were similar in terms of age, averaging about 40 years old, and most of the participants were female.

Compared to the controls, scleroderma patients had specific antibodies against EBV significantly more frequently. Antibodies are proteins made by the immune system to respond to infectious threats that can target a specific viral protein.

In particular, scleroderma patients had significantly higher rates of IgM antibodies against the EBV proteins VCA gp125, VCA p19, EBNA1, p22, and EA-D. They also had higher rates of IgG antibodies to p22 and EA-D.

IgM and IgG are two different classes of antibodies that are produced at different points in the immune response. According to the researchers, this pattern of elevated antibodies in scleroderma patients suggests these individuals are more likely to experience reactivation of latent EBV infection.

“Our study showed a higher frequency of class IgM antibodies against VCA gp125, VCA p19, EBNA1, p22, EA-D and class IgG antibodies against p22 and EA-D reactivities in SSc patients compared to controls , suggesting a strong sense of humor [antibody-driven] Response to EBV antigens and a significant association of viral reactivation with SSc patients,” the scientists wrote.

However, when the researchers tested the participants’ blood for EBV DNA, only 2% of the scleroderma patients tested positive, as did 2% of the controls. This suggests that despite the antibody pattern suggesting greater reactivation in scleroderma patients, these individuals do not have higher levels of the virus itself in their blood.

These results suggest that the elevated levels of anti-EBV antibodies “are not caused by increased circulating viral load or an inability to control systemic EBV infection,” the researchers wrote.

Remarkable results

This finding is particularly noteworthy given that in other autoimmune diseases such as MS, the main types of cells involved in disease-related EBV reactivation are B cells, a type of immune cell found primarily in the blood. If EBV reactivation occurs in the B cells of scleroderma patients, one would expect that these patients would have higher levels of viral DNA in their blood, contrary to the researchers’ findings.

“Thus, the study indicates serological activation of EBV (reactivation stage) in SSc patients in the absence of EBV DNA in the blood, suggesting that the EBV reservoir is present elsewhere,” the team wrote.

Scientists speculated that EBV reactivation could result in pro-scarring responses in its cellular target/reservoir.

“The source of the blood anti-EBV humoral response should be investigated as the cellular source is unknown, which is a limitation of our study,” the researchers wrote.

Another notable limitation is that all SSc patients in this study were taking immunosuppressive drugs to manage their disease. While other studies have generally not shown that such treatment can induce EBV reactivation, the researchers noted that they “cannot rule out the possible role of immunosuppression in EBV reactivation in this study.”