Epstein-Barr Virus and Systemic Lupus Erythematosus

Abstract

<jats:p>The etiology of SLE is not fully established. SLE is a disease with periods of waning disease activity and intermittent flares. This fits well in theory to a latent virus infection, which occasionally switches to lytic cycle, and EBV infection has for long been suspected to be involved. This paper reviews EBV immunobiology and how this is related to SLE pathogenesis by illustrating uncontrolled reactivation of EBV as a disease mechanism for SLE. Studies on EBV in SLE patients show enlarged viral load, abnormal expression of viral lytic genes, impaired EBV-specific T-cell response, and increased levels of EBV-directed antibodies. These results suggest a role for reactivation of EBV infection in SLE. The increased level of EBV antibodies especially comprises an elevated titre of IgA antibodies, and the total number of EBV-reacting antibody isotypes is also enlarged. As EBV is known to be controlled by cell-mediated immunity, the reduced EBV-specific T-cell response in SLE patients may result in defective control of EBV causing frequent reactivation and expression of lytic cycle antigens. This gives rise to enhanced apoptosis and amplified cellular waste load resulting in activation of an immune response and development of EBV-directed antibodies and autoantibodies to cellular antigens.</jats:p>

How compelling are the data for Epstein–Barr virus being a trigger for systemic lupus and other autoimmune diseases?

“…An altered infection pattern with poor control of the latent EBV infection and exacerbations of an active lytic cycle has been established. Previous findings comprise high viral loads, increased EBV mRNA expression, and elevated humoral responses against EBV (reviewed in [11,15,16]). Already in 1971 an association was demonstrated by increased EBV antibody titres in SLE patients [15,17].…”

“…Already in 1971 an association was demonstrated by increased EBV antibody titres in SLE patients [15,17]. Numerous studies confirmed higher frequencies and elevated titres of EBV-directed antibodies, against lytic cycle antigens, in SLE patients compared to healthy controls (HCs), indicating frequent EBV reactivations (reviewed in [11,18] The decreased control of EBV in SLE patients was also lately demonstrated by the presence of EBV DNA detected by PCR in serum from SLE patients [26], and by several case reports. A 50-year-old woman diagnosed with SLE (and concurrent autoimmune hepatitis) developed chronic active EBV infection with EBER-positive lymphocytes found in both liver and gastric mucosal biopsies and in high concentrations in the CD4+ T-cells in the blood [27].…”

“…However, 30-70% of individuals acquiring a primary EBV infection during adolescence develop infectious mononucleosis (IM) [10] with symptoms resembling those of SLE [11,12,13]. Following primary infection, EBV persists in a latent form in memory B-cells, evading the host's immune system and preventing apoptosis of the infected cells [8].…”

Avaliação diagnóstica das infecções por vírus Epstein-Barr, parvovírus B19 e vírus linfotrópico de células T humanas em pacientes portadores de lúpus eritematoso sistêmico em hospital de referência do Estado do Pará, Brasil

“…A associação da infecção por EBV e o LES tem sido relatada em vários estudos, mediante evidências sorológicas e moleculares 22,49,50 . Em pacientes com a doença, há uma soroconversão mais rápida para EBV e um valor de carga viral superior quando comparados a indivíduos infectados pelo vírus e sem LES 51,52 .…”

Viruses: Cofactors in Idiopathic Pulmonary Fibrosis

“…It is one of the most common human viruses present in all populations and latently infects nearly 95% of the people via saliva contact [17]. A number of studies have suggested a possible connection with EBV as a persistent antigenic stimulus in IPF.…”