Clinical Chemistry
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Clinical Chemistry 51: 47-55, 2005. First published September 13, 2004; 10.1373/clinchem.2004.031229
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(Clinical Chemistry. 2005;51:47-55.)
© 2005 American Association for Clinical Chemistry, Inc.


Proteomics and Protein Markers

Protein Chip Array Profiling Analysis in Patients with Severe Acute Respiratory Syndrome Identified Serum Amyloid A Protein as a Biomarker Potentially Useful in Monitoring the Extent of Pneumonia

Timothy T.C. Yip1,2, Johnny W.M. Chan2,2, William C.S. Cho1, Tai-Tung Yip5, Zheng Wang5, Ting-Lok Kwan3, Stephen C.K. Law1,a, Dominic N.C. Tsang4, John K.C. Chan4, King-Chung Lee4, Wai-Wai Cheng1, Victor W.S. Ma1, Christine Yip5, Cadmon K.P. Lim1, Roger K.C. Ngan1, Joseph S.K. Au1, Angel Chan4 and Wilina W.L. Lim6 and Queen Elizabeth Hospital/Hong Kong Government Virus Unit/Ciphergen SARS Proteomics Study Group7

Departments of1 Clinical Oncology, 2 Medicine, 3 Diagnostic Radiology, and 4 Pathology, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, The People’s Republic of China.
5 Ciphergen Biosystems Incorporation, Fremont, CA.
6 Hong Kong Government Virus Unit, Department of Health, Hong Kong Special Administrative Region, The People’s Republic of China.
7 Joint Queen Elizabeth Hospital/Hong Kong Government Virus Unit/Ciphergen Biosystems Incorporation SARS Proteomics Study Group.

aAddress correspondence to this author at: Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Rd., Kowloon, Hong Kong SAR. Fax 852-23594782; e-mail lawck{at}ha.org.hk.

Background: A new strain of coronavirus (CoV) has caused an outbreak of severe acute respiratory syndrome (SARS), with 8098 individuals being infected and 774 deaths worldwide. We carried out protein chip array profiling analysis in an attempt to identify biomarkers that might be useful in monitoring the clinical course of SARS patients.

Methods: We performed surface-enhanced laser desorption ionization time-of-flight mass spectrometry on 89 sera collected from 28 SARS patients, 72 sera from 51 control patients with various viral or bacterial infections, and 10 sera from apparently healthy individuals.

Results: Nine significantly increased and three significantly decreased serum biomarkers were discovered in the SARS patients compared with the controls. Among these biomarkers, one (11 695 Da) was identified to be serum amyloid A (SAA) protein by peptide mapping and tandem mass spectrometric analysis. When we monitored the SAA concentrations longitudinally in 45 sera from four SARS patients, we found a good correlation of SAA concentration with the extent of pneumonia as assessed by a serial chest x-ray opacity score. Increased SAA occurred in three of four patients at the time of extensive pneumonia as indicated by high x-ray scores. Over the course of gradual recovery in two patients, as assessed clinically and radiologically, SAA concentrations gradually decreased. In the third patient, the concentrations were initially increased, but were further increased with superimposed multiple bacterial infections. SAA was not markedly increased in the fourth patient, who had low x-ray scores and whose clinical course was relatively mild.

Conclusions: Protein chip array profiling analysis could be potentially useful in monitoring the severity of disease in SARS patients.




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