Background In our studies of the relationship of the association of Epstein-Barr virus (EBV) infection with SLE we have also found an association of the anti-EBV Epstein-Barr Nuclear Antigen 1 (EBNA1) with SLE.1 Previously, we found that the anti-60kd Ro/SSA and anti-Sm B/B’ autoantibody responses were initiated at autoantigenic epitopes that cross-reacted with antigenic epitopes from EBNA1. Anti-Sm D and anti-C1q also bind EBNA1, constituting two additional examples in SLE. The structure of EBNA1 is unique in the known biological universe and profoundly inhibits the anti-EBNA1 CD8 T cell response, providing a basis for considering specific effects of this antigen on the human host immune response.
Methods Literature search and combining available data to present summary results.
Results Recent studies establish that not only was anti-GlialCAM autoimmunity pathogenic in multiple sclerosis (MS) but also show that these autoantibodies bound EBNA1.2 A literature search revealed three EBNA1 cross reacting autoantigens in MS: αB crystallin, myelin basic protein, and anoctamin 2. In addition, accessible serologic data are consistent with anti-EBNA1 being increased in MS relative to EBV-infected controls, as they are in SLE, therefore, in aggregate suggesting that our model extends to MS. There is also evidence for a potential EBNA1 binding by anti-citrullinated peptide antibodies of rheumatoid arthritis by citrullinating Arginines of EBNA1.
Conclusions These and other observations have led to a theory for the etiology and initiation of autoantibodies in SLE in which the anti-EBNA1 heteroimmune response constitutes the usual initiating humoral immune response for SLE autoantibodies. With two such different disorders potentially originating from the anti-EBNA1 response, one wonders whether such a mechanism may operate in other disorders. These findings present a possible human host immune response basis for the origin of lupus.
Laurynenka V, et al. Front Immunol 2022;13:830993.
Lanz TV, et al. Nature 2022;603:321.
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