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. 2023 Mar 24;24(7):6156.
doi: 10.3390/ijms24076156.

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement

Rada Miskovic  1   2 , Andja Cirkovic  3 , Danijela Miljanovic  4 , Ivica Jeremic  2   5 , Milka Grk  6 , Milica Basaric  5 , Ivana Lazarevic  4 , Maja Stojanovic  1   2 , Aleksandra Plavsic  1   2 , Sanvila Raskovic  1   2 , Ana Banko  4
Affiliations

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement

Rada Miskovic et al. Int J Mol Sci. .

Abstract

Although Epstein-Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

Keywords: EBV reactivation; Epstein–Barr virus (EBV); SLE remission; anti-EA (D) IgM; biomarker; lupus low disease activity state; predictor; systemic lupus erythematosus (SLE).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Violin plots for comparison of anti-EBV antibodies’ titer level during the follow up (a) anti-EA (D) IgG; (b) anti-VCA IgG; (c) anti-EBNA-1 IgG; (d) anti-EA (D) IgM; (e) anti-VCA IgM.
Figure 2
Figure 2
ROC curve analysis of C3 level in differentiating transition from active into latent EBV infection.
See this image and copyright information in PMC

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