Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients!
Our study on autoantibodies in TBE patients has now been published in the Journal of Experimental Medicine! This work was done in close collaboration with the Laboratory of Human Genetics of Infectious Diseases under the direction of Jean-Laurent Casanova and many other great co-authors.
In the past, auto-Abs against type I IFNs have been shown to underlie about 15% of critical cases of COVID19. Recently, the Casanova lab has shown that auto-Abs against type I IFNs predispose ~40% of patients to West Nile virus (WNV) encephalitis following infection with WNV.
In this new study, we investigated four cohorts of TBEV infection from Austria, the Czech Republic, France, and Italy. We show that 10% of the severe TBE cases have circulating auto-Abs neutralizing type I IFNs. By contrast, <1% of the mild and moderate cases had these auto-Abs, similar to their prevalence in the general population. Individuals carrying these auto-Abs are up to 20 times more at risk to develop severe TBE, when compared with those without auto-Abs, depending on the combination and concentration of IFNs neutralized. Interestingly, auto-Abs found in our patients mainly neutralize IFN-ω, unlike in the previous infections we studied. These auto-Abs are not triggered by TBEV infection, and they are not transient. Moreover, these auto-Abs neutralize the protective effect of IFN-α2 and IFN-ω in Vero cells infected by TBEV in vitro.
Read this whole fascinating story!
