Autoantibodies against the prion protein in individuals with PRNP mutations

Objective. To determine whether naturally occurring autoantibodies against the prion protein are present in individuals with genetic prion disease mutations and controls, and if so, whether they are protective against prion disease. 

Methods. In this case-control study, we collected 124 blood samples from individuals with a variety of pathogenicPRNPmutations and 78 control individuals with a positive family history of genetic prion disease but lacking disease-associatedPRNPmutations. Antibody reactivity was measured using an indirect ELISA for the detection of human IgG1-4 antibodies against wild-type human prion protein. Multivariate linear regression models were constructed to analyze differences in autoantibody reactivity between a) PRNPmutation carriers versus controls and b) asymptomatic versus symptomatic PRNPmutation carriers. Robustness of results was examined in matched cohorts.

Results. We found that antibody reactivity was present in a subset of both PRNPmutation carrie...