Table 4.

Peculiar alterations of EBV-specific immune response in SLE.

Type of Alteration	Comment	References
Reduced EBV-specific CD8+ lymphocyte response and increased CD4+ lymphocyte response	Impaired cytotoxic potential of EBV-specific CD8+ lymphocytes is due to a SLE-intrinsic defect and is probably the primum movens of altered immune response	[78,79,80,81,82,83]
Decreased Th17 and Treg response	Imbalance between Th17 and T reg is a major cause of AIDs and decrease in Th17 may be an important feature of EBV/CMV infection.	[84]
Elevated EBV viral load in B cells and PBMC and aberrant expression of viral mRNAs of lytic (BZLF-1, BLLF-1) and latent phase proteins (LMP-1, LMP-2 and EBNA-1)	It is due to impaired control of EBV infection by CTLs, with frequent viral reactivations (BZLF-1, BLLF-1) and abnormal latency state (LMP-1, LMP-2, EBNA-1)	[82,85,86,87,88,89]
Elevated EBV seroprevalence	EBV seroprevalence is very high especially in certain populations, in which prior EBV infection appears necessary to develop SLE	[90,91,92,93,94]
Elevated titers of antibody against early lytic (EA/D; EA/R) and latent (EBNA) EBV antigens	This could represent an enhanced compensatory humoral response secondary to an inadequate T-cell control of a chronic EBV infection, with frequent reactivations. It can be associated with production of autoantibodies.	[75,89,91,95,96,97,98]
Elevated prevalence of IgA against EA/D antigen and coexistence of different EBV-specific immunoglobulin isotypes	It may indicate disseminated EBV infection, with higher lytic rate of epithelial cells (IgA) and lymphocytes (IgG).	[89,99,100]
Temporal relationship between anti-EBV antibodies and SLE manifestations	Anti-EBV humoral response can precede SLE onset or flareups. It identifies first-degree unaffected family members of SLE patients who are at risk of transitioning to SLE	[75,101,102,103]
Coexistence of anti-EBV antibodies and SLE-specific autoantibodies	Cross-reactivity between EBV- and self-antigens explains associations between anti-EA/D and anti-Ro/anti-La antibodies, also observed in Sjögren’s syndrome, and between anti-EBNA-1 and anti-C1q.	[74,93,104,105]