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

Ana Banko; Andja Cirkovic; Rada Miskovic; Ivica Jeremic; Milka Grk; Milica Basaric; Ivana Lazarevic; Sanvila Raskovic; Aleksa Despotovic; Danijela Miljanovic

doi:10.3389/fimmu.2023.1307589

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

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

Authors

Ana Banko¹, Andja Cirkovic², Rada Miskovic^{3

4}, Ivica Jeremic^{4

5}, Milka Grk⁶, Milica Basaric⁵, Ivana Lazarevic¹, Sanvila Raskovic^{3

4}, Aleksa Despotovic², Danijela Miljanovic¹

Affiliations

¹ Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
² Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
³ Clinic of Allergy and Immunology, University Clinical Center of Serbia, Belgrade, Serbia.
⁴ Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁵ Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁶ Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Viral
Epstein-Barr Virus Infections* / complications
Epstein-Barr Virus Infections* / epidemiology
Herpesvirus 4, Human
Humans
Immunoglobulin G
Lupus Erythematosus, Systemic* / complications
Lupus Erythematosus, Systemic* / diagnosis

Substances

Antigens, Viral
Immunoglobulin G

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The research was funded by the Science Fund of the Republic of Serbia, PROMIS, grant number 6060866, ROLERS.