Epstein-Barr Virus Reactivation May Be a Predictor of Remission in SLE

Epstein-Barr virus (EBV) reactivation may be a predictor of achieving remission or lupus low disease activity state (LLDAS) in patients with systemic lupus erythematosus (SLE) with cutaneous involvement, according to study results published in International Journal of Molecular Sciences.

Researchers examined markers of humoral response to lytic and latent EBV antigens and the presence of EBV DNA to assess the link between EBV reactivation and SLE remission or LLDAS over a 6-month period.

Anti-EBV antibody and EBV DNA tests were conducted twice every 6 months among participants with the active form of SLE.

The primary outcome was SLE remission or LLDAS after 6 months to follow-up.

Remission was defined as having a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 0, and LLDAS was defined as a composite SLEDAI-2K score of 4 or lesser, with no significant involvement of organ systems, and physician global assessment (PGA) of less than 1.

This study included 51 patients with active SLE, of whom 49 were included in the final analysis. In the final cohort, 94% were women, had a mean age of 42.49±13.06 years, and a median disease duration of 5 years.

During the follow-up period, the majority of patients experienced a significant improvement or complete resolution in their active mucocutaneous (78%), musculoskeletal (74%), and hematologic (69%) manifestations. Both disease activity scores (SLEDAI-2K and PGA) showed significant decreases (P <.001 for both scores), with a median reduction of 6.0 (IQR, 3.0-9.25) for SLEDAI-2K and 0.81 (IQR, 0.45-1.23) for PGA. In 60% of patients, the total SLEDAI-2K score was 4 or lesser; in 82% of patients, the PGA score was 1 or lesser. A total of 54% of patients had their prednisone dose reduced to 10 mg or lesser from their stable prednisone dose of less than 20 mg/day.

At the end of the follow-up period, active EBV infection was identified in 45% of patients with active SLE at baseline, with 77% transitioning to latent EBV infections at 6 months (P <.001).

Independent predictors of remission and LLDAS in patients with mucocutaneous manifestations (P =.042) and rash only (P =.023) were noted to be a higher titer of anti-EA(D) immunoglobulin (Ig)M antibodies and the presence of anti-EA(D) IgM antibodies. Higher complement 3 (C3) level was an independent predictor of the transition to latent EBV infection (P =.027). In patients with active SLE, EBV reactivation was common, and after 6months, the majority of patients transitioned to latent EBV infection.

An estimated cutoff value of at least 0.780 g/L with a sensitivity of 70.6% and specificity of 75.0% (area under the curve [AUC], 0.756; P =.003) could identify patients with active SLE likely to transition to latent EBV infection after 6 months.

One of the study limitations included that the 6-month follow-up period may not have been enough time for patients with severe disease to achieve remission. 

According to the study authors, “Further data demonstrating a specific link between EBV and SLE may provide deeper insight into new targeted lupus therapies.”