Urinary alpha1-antichymotrypsin: a biomarker of prion infection.
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.
Miele
Gino
G
Department of Pathology, UniversitätsSpital Zürich, Institute of Neuropathology, Zürich, Switzerland. g.miele@dundee.ac.uk
Seeger
Harald
H
Marino
Denis
D
Eberhard
Ralf
R
Heikenwalder
Mathias
M
Stoeck
Katharina
K
Basagni
Max
M
Knight
Richard
R
Green
Alison
A
Chianini
Francesca
F
Wüthrich
Rudolf P
RP
Hock
Christoph
C
Zerr
Inga
I
Aguzzi
Adriano
A
D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000652:urine; D001921:Brain / Q000378:metabolism; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis / Q000378:metabolism; D055316:Cystatin C / Q000134:cerebrospinal fluid; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D017096:Prion Diseases / Q000175:diagnosis* / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D000514:alpha 1-Antichymotrypsin / Q000134:cerebrospinal fluid / Q000235:genetics / Q000652:urine*
D015415:Biomarkers; D055316:Cystatin C; D015843:Serpins; D000514:alpha 1-Antichymotrypsin