Systemic lupus erythematosus (SLE or lupus) is a complex disease with a multifactoral etiology, with genetic, hormonal, and environmental influences. Molecular mimicry as a result of
viral infection may contribute to the development of lupus. The pattern of
autoantibody development in lupus is consistent with initiation through molecular mimicry, as the initial autoantigenic
epitopes that have been observed are limited and cross-reactive with
viral proteins.
Autoantibody specificity may then later diversify to other
autoantigens through
B-cell epitope spreading. Epstein-Barr virus (EBV) is an excellent candidate to be involved in molecular mimicry in lupus.
EBV infection has been associated with lupus through serological and
DNA studies.
Infection with EBV results in the production of the
viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1),
antibodies against which cross-react with lupus-associated
autoantigens, including Ro, Sm B/B', and Sm D1, in lupus patients. The immune response against EBV, and
EBNA-1 in particular, differs among lupus patients and healthy controls, with controls maintaining a limited humoral response and failing to produce long-standing cross-reactive
antibodies. We hypothesize that the humoral immune response to
EBNA-1 in susceptible individuals leads to the generation of cross-reactive
antibodies. Through the process of
epitope spreading, these cross-reactive
antibodies target additional, non-cross reactive autoepitopes, spread to additional
autoantigens, and become pathogenic, leading eventually to clinical lupus. This paper reviews some of the current literature supporting roles for EBV exposure and
epitope spreading in SLE.