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. 2023 Dec 7:14:1307589.
doi: 10.3389/fimmu.2023.1307589. eCollection 2023.

Epstein-Barr virus infection as potential indicator of the occurrence and clinical presentation of systemic lupus erythematosus

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

Epstein-Barr virus infection as potential indicator of the occurrence and clinical presentation of systemic lupus erythematosus

Ana Banko et al. Front Immunol. .

Abstract

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated.

Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients.

Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported.

Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus.

Keywords: EA(D) IgG; EBNA1; Epstein-Barr virus (EBV); LMP1; anti-EBV antibodies; marker; systemic lupus erythematosus (SLE).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Anti-EBV-EBNA1 IgG antibodies in SLE patients and controls (p<0.001).
Figure 2
Figure 2
Anti-EBV-CA IgG antibodies in SLE patients and controls (p=0.003).
Figure 3
Figure 3
Anti-EBV-CA IgM antibodies in SLE patients and controls (p<0.001).
Figure 4
Figure 4
Anti-EBV-EA(D) IgG antibodies in SLE patients and controls (p<0.001).
Figure 5
Figure 5
Anti-EBV-EA(D) IgM antibodies in SLE patients and controls (p=0.012).
See this image and copyright information in PMC

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