Urinary alpha1-antichymotrypsin: a biomarker of prion infection

TitleUrinary alpha1-antichymotrypsin: a biomarker of prion infection
Publication TypeJournal Article
Year of Publication2008
AuthorsMiele G, Seeger H, Marino D, Eberhard R, Heikenwalder M, Stoeck K, Basagni M, Knight R, Green A, Chianini F, Wuthrich RP, Hock C, Zerr I, Aguzzi A
JournalPLoS One
ISSN1932-6203 (Electronic)
Accession Number19057641
Keywordsalpha 1-Antichymotrypsin / cerebrospinal fluid / genetics / *urine, Animals, Biological Markers / cerebrospinal fluid / urine, Brain / metabolism, Creutzfeldt-Jakob Syndrome / diagnosis / metabolism, Cystatin C / cerebrospinal fluid, Humans, Mice, Mice, Inbred C57BL, Microarray Analysis, Prion Diseases / *diagnosis / metabolism, Serpins / genetics / metabolism

The occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. However, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. Sensitive biomarkers may help meeting this need. Here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. We found that alpha(1)-antichymotrypsin (alpha(1)-ACT) was highly upregulated in brains of scrapie-infected mice. Furthermore, alpha(1)-ACT levels were dramatically increased in urine of patients suffering from sporadic Creutzfeldt-Jakob disease, and increased progressively throughout the disease. Increased alpha(1)-ACT excretion was also found in cases of natural prion disease of animals. Therefore measurement of urinary alpha(1)-ACT levels may be useful for monitoring the efficacy of therapeutic regimens for prion disease, and possibly also for deferring blood and organ donors that may be at risk of transmitting prion infections.

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