Potential role of the Epstein-Barr virus in systemic lupus erythematosus autoimmunity

Abstract

Objective: To investigate the possibility that Epstein-Barr virus (EBV), the agent of infectious mononucleosis (IM), may play a role in systemic lupus erythematosus (SLE).

Methods: EBV was searched for by PCR and by culture isolation in oropharyngeal lavage fluids of 15 SLE patients and, as controls, in 13 IM patients and in 28 healthy individuals with past EBV infection. Computer analysis was performed to select an antigenic domain of the virus-encoded nuclear antigen EBNA-2, in order to set up a synthetic peptide-based immunoassay. IgG antibodies to a 20-amino acid synthetic peptide derived from the selected domain of EBNA-2 (354GRGKGKSRDKQRKPGGPWRP373) were titrated in the sera of 20 SLE patients, 24 IM patients and 12 healthy subjects.

Results: EBV type 1 DNA was demonstrated by PCR in the oropharyngeal secretions of 8 SLE patients and the virus was isolated from 6 DNA-positive specimens. Moreover, 50% of the patients with SLE and 100% of the patients in the acute phase of IM, but none of the EBV-seropositive normal individuals, produced IgG antibodies to the EBNA-2-derived synthetic peptide. Computer analysis revealed a high degree of homology between the EBNA-2 354GRGKGKSRDKQRKPGGPWRP373 sub-sequence and the antigenic C-terminal domain 101GRGRGRGRGRGRGRGGPRR119 of the SmD1 ribonucleoprotein, a target of autoantibodies in a portion of SLE patients.

Conclusion: We suggest the possibility that EBV may establish a persistent infection at least in a certain number of SLE patients. The antibodies elicited by the viral antigen EBNA-2 may cross-react with SmD1, thus indicating a role of EBV-specific immune responses in the outcome of SmD1 autoantibodies in SLE patients.