Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay
| Autor: | Michael Farmer, John Collinge, Tracy Campbell, Graham S. Jackson, Paul Tavares, Julie Ann Edgeworth, Simon Mead, Jon Beck, Peter Rudge, Jessica Lowe, Anita Sicilia |
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| Rok vydání: | 2011 |
| Předmět: |
Blood transfusion
Serial dilution medicine.diagnostic_test business.industry medicine.medical_treatment General Medicine Human brain medicine.disease Virology Asymptomatic nervous system diseases Central nervous system disease Degenerative disease medicine.anatomical_structure mental disorders medicine Blood test medicine.symptom business Whole blood |
| Zdroj: | The Lancet. 377:487-493 |
| ISSN: | 0140-6736 |
| DOI: | 10.1016/s0140-6736(10)62308-2 |
| Popis: | Summary Background Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder originating from exposure to bovine-spongiform-encephalopathy-like prions. Prion infections are associated with long and clinically silent incubations. The number of asymptomatic individuals with vCJD prion infection is unknown, posing risk to others via blood transfusion, blood products, organ or tissue grafts, and contaminated medical instruments. We aimed to establish the sensitivity and specificity of a blood-based assay for detection of vCJD prion infection. Methods We developed a solid-state binding matrix to capture and concentrate disease-associated prion proteins and coupled this method to direct immunodetection of surface-bound material. Quantitative assay sensitivity was assessed with a serial dilution series of 10 −7 to 10 −10 of vCJD prion-infected brain homogenate into whole human blood, with a baseline control of normal human brain homogenate in whole blood (10 −6 ). To establish the sensitivity and specificity of the assay for detection of endogenous vCJD, we analysed a masked panel of 190 whole blood samples from 21 patients with vCJD, 27 with sporadic CJD, 42 with other neurological diseases, and 100 normal controls. Samples were masked and numbered by individuals independent of the assay and analysis. Each sample was tested twice in independent assay runs; only samples that were reactive in both runs were scored as positive overall. Findings We were able to distinguish a 10 −10 dilution of exogenous vCJD prion-infected brain from a 10 −6 dilution of normal brain (mean chemiluminescent signal, 1·3×10 5 [SD 1·1×10 4 ] for vCJD vs 9·9×10 4 [4·5×10 3 ] for normal brain; p Interpretation These initial studies provide a prototype blood test for diagnosis of vCJD in symptomatic individuals, which could allow development of large-scale screening tests for asymptomatic vCJD prion infection. Funding UK Medical Research Council. |
| Databáze: | OpenAIRE |
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