NR AFQN
AU Hsich,G.; Kenney,K.; Gibbs,C.J.Jr.; Lee,K.H.; Harrington,M.G.
TI The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies
QU The New England Journal of Medicine 1996 Sep 26; 335(13): 924-30
KI ACP J Club. 1997 Mar-Apr;126(2):45 N Engl J Med. 1996 Sep 26;335(13):963-5. PMID: 8782506 N Engl J Med. 1997 Mar 20;336(12):873-4; discussion 874-5. PMID: 9072684 N Engl J Med. 1997 Mar 20;336(12):874; discussion 874-5. PMID: 9072685
PT journal article
AB
BACKGROUND: There is no practical and reliable premortem test for Creutzfeldt-Jakob disease and the related transmissible spongiform encephalopathies. Two proteins, designated 130 and 131, which have been detected in low concentrations in cerebrospinal fluid from patients with Creutzfeldt-Jakob disease, appear to be sensitive and specific markers for the disease. Attempts to identify these proteins, however, have been unsuccessful. We hypothesized that they may be present in the normal brain.
METHODS: We detected proteins 130 and 131 in normal human brain, partially sequenced their amino acids, and found that they matched the brain protein known as 14-3-3. We then developed a simple, rapid immunoassay for this protein and tested it in cerebrospinal fluid samples from 71 humans and 30 animals with spongiform encephalopathies and in control samples from 186 humans and 94 animals.
RESULTS: The immunoassay detected the 14-3-3 protein in cerebrospinal fluid from 68 of the 71 patients with Creutzfeldt-Jakob disease (96 percent, 95 percent confidence interval, 92 to 99 percent). Among 94 patients with other dementias, the specificity was 96 percent. If one excludes the three patients with dementia who had strokes within one month before testing, the specificity was 99 percent. The test was positive in 12 of 24 patients with viral encephalitis. In animals the sensitivity of the assay was 87 percent and the specificity was 99 percent.
CONCLUSION: In patients with dementia, a positive immunoassay for the 14-3-3 brain protein in cerebrospinal fluid strongly supports a diagnosis of Creutzfeldt-Jakob disease. This finding, however, does not support the use of the test in patients without clinically evident dementia.
IN Die Autoren isolierten aus normalem menschlichem Gehirn die von der Rückenmarksflüssigkeit von CJD-Patienten bekannten Proteine 130 und 131 und sequenzierten sie an. Durch partielle Proteinsequenzierung stellten die Autoren fest, dass die nach zweidimensionaler Gelelektrophorese in der Rückenmarksflüssigkeit von CJD-Patienten aufgefallenen Proteine 130 und 131 zur Familie der 14-3-3-Proteine gehörten. Anschließend entwickelten sie einen einfachen und schnellen Immunoassay und validierten ihren Test mit Rückenmarksflüssigkeit von 71 Patienten und 30 Tiere mit spongiformen Enzephalopathien, sowie Negativkontrollen von 186 Menschen und 94 Tieren. Der Immunoassay verlief bei 68 von 71 Patienten mit spongiformen Enzephalopathien, aber auch bei 3 binnen eines Monats nach einer Embolie im Hirn untersuchten, sowie bei 12 von 24 Menschen mit viralen Enzephalopathien positiv. Der 14-3-3-Test kann somit nicht als wirklich spezifischer CJK-Test gelten.
MH Amino Acid Sequence; Animal; Biological Markers/cerebrospinal fluid; Cerebrospinal Fluid Proteins/*analysis/chemistry; Creutzfeldt-Jakob Syndrome/cerebrospinal fluid/*diagnosis; Dementia/cerebrospinal fluid/diagnosis; Electrophoresis, Gel, Two-Dimensional; Human; Immunoassay/methods; Molecular Sequence Data; Prion Diseases/cerebrospinal fluid/diagnosis; Proteins/*analysis/chemistry; Sensitivity and Specificity; Support, U.S. Gov't, P.H.S.
AD
Gary Hsich, Kimbra Kenney and Clarence J. Gibbs, Jr. from the Laboratory of Central Nervous System Studies, National Institutes of Health, Bethesda, Md.
Kelvin H. Lee and Michael G. Harrington from the Biology Division, California Institute of Technology, Pasadena.
Address reprint requests to Dr. Gibbs at the Laboratory of Central Nervous System Studies, Basic Neurosciences Program, Division of Intramural Research, Bldg. 36, Rm. 4A05, 9000 Rockville Pike, Bethesda, MD 20892-4122, or to Dr. Harrington at Mailstop 139/74, California Institute of Technology, Pasadena, CA 91125, USA
SP englisch
PO USA
OR Prion-Krankheiten H