Even the control cohort seroprevalence is lower than expected. Very surprised they didn't look at EBNA1 serologies, I think it's hard to come to strong conclusions without it

I think a major strength of this study is it provides a reasonable explanation how EBV could interact with other factors to propagate autoimmunity. It will be important to determine how EBV differentially alters specific B cell populations in other autoimmune diseases like MS 8/

They propose “EBV may directly infect anti-EBNA1 B cells with autoimmune cross-reactivity in SLE (as well as infect other autoreactive antinuclear antigen B cells), which may then serve as APCs and enhance and orchestrate the pathogenic autoimmune response in SLE ” 7/

Their interpretation of this critical finding: “The fact that antinuclear antigen EBV+ B cells belong to the same clonal family as other antinuclear antigen EBV− B cells suggests that EBV infection occurred during an ongoing autoimmune response” 6/

Importantly, antibodies cloned from EBV-infected B cells in MS patients and healthy controls showed no such reactivity to antinuclear antigens 5/

The authors show a significant fraction of EBV-infected B cells in SLE produce antinuclear antigen-specific antibodies, some of which cross-bind EBNA1. Furthermore, they found EBV-negative clonally-related B cells that also produce antinuclear antigen-specific antibodies 4/

One of the major challenges in the field is how EBV, a highly prevalent virus, can lead to distinct types of autoimmunity in only a subset of infected individuals. One way to potentially explain this is by considering the antigen specificity of EBV-infected B cells 3/

Their core findings are the identification of increased EBV expression in antinuclear antigen-reactive B cells in SLE leading to increased antigen presentation to autoreactive Tfh, which propagates a loop of autoimmunity 2/