Novel prototype assay provides high specificity, sensitivity in detecting Creutzfeldt-Jakob disease
A new prototype blood test for variant Creutzfeldt-Jakob disease provides high specificity and sensitivity, and may have potential value in screening for this infection in prion-exposed populations, according to a feasibility study.
Moreover, the study found that the test’s lack of cross-reactivity and false-positive results support its use in patient screenings, according to findings published today in JAMA Neurology.
The retrospective, cross-sectional study tested the novel assay on anonymous blood samples of healthy donors acquired from the American Red Cross (n= 5,000) and from the National Health Service Blood and Transplant (n=200). To assess the possible effects of cross-reacting species on the test’s specificity, the researchers also evaluated blood samples from patients with a range of non-prion neurodegenerative diseases (n=352). Also tested were samples for which a prion disease diagnosis was likely (n=105), obtained from National Prion Clinic (NPC) referrals, as well as samples from 10 patients with confirmed variant Creutzfeldt-Jakob disease (vCJD).
The study’s main outcome was the existence of vCJD infection as determined by the prototype test.
The study found that among the healthy, presumed-negative American donor samples, the assay had 100% specificity (95% CI, 99.93%-100%) and this specificity was repeated in the healthy UK cohort (100% specificity; 95% CI, 98.2%-100%). There were no positive test results among the potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases (100% specificity; 95% CI, 98.9%-100%). Two of the samples, in which a prion disease diagnosis was considered probable, had positive test results (98.1% specificity; 95% CI, 93.3%-99.8%). These patients had sporadic CJD.
While the study’s main objective was the assay’s specificity, the researchers also confirmed the test’s sensitivity in detecting vCJD-infected blood. Using masked samples, the assay was able to accurately detect 100% of exogenous-spiked samples and 70% of samples from patients with vCJD. This confirmed but did not refine prior sensitivity estimates, according to the researchers, who also said that these findings “rigorously validated” the specificity of the prototype vCJD test.
“Most importantly, the prototype vCJD assay has sufficient performance to justify now screening a large U.K. population sample and at-risk groups to produce an initial estimate of the level of prionemia in the U.K. blood donor population,” the researchers wrote. “A blood prevalence study would provide essential information for policy makers for deciding if routine vCJD screening is needed for blood, tissue, and organ donations, and patients prior to high-risk surgical procedures.”
Disclosure: Collinge serves as a director and both Collinge and Jackson are shareholders of D-Gen Ltd (London), a company working in the field of prion disease diagnosis, decontamination, and therapeutics.