Received on October 6, 2005
Accepted on December 19, 2005

Proteomics and Protein Markers

Serum Proteomic Fingerprints of Adult Patients with Severe Acute Respiratory Syndrome

¹ Centre for Emerging Infectious Diseases and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR
² Centre for Emerging Infectious Diseases and Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR
³ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR
⁴ Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR
⁵ Department of Biology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR

^* To whom correspondence should be addressed. E-mail: tcwpoon{at}cuhk.edu.hk.

Background: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus strain, SARS-CoV. Specific proteomic patterns might be present in serum in response to the infection and could be useful for early detection of the disease.

Methods: Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, serum proteins of 39 patients with early-stage SARS infection and 39 non-SARS patients who were suspected cases during the SARS outbreak period were profiled and compared. Proteomic patterns associated with SARS were identified by bioinformatic and biostatistical analyses. Features of interest were then purified and identified by tandem mass spectrometry.

Results: Twenty proteomic features were significantly different between the 2 groups. Fifteen were increased in the SARS group, and 5 were decreased. Their concentrations were correlated with 2 or more clinical and/or biochemical variables. Two were correlated with the SARS-CoV viral load. Hierarchical clustering analysis showed that a majority of the SARS patients (95%) had similar serum proteomic profiles and identified 2 subgroups with poor prognosis. ROC curve analysis showed that individual features were potential biomarkers for SARS diagnosis (areas under ROC curves, 0.733-0.995). The largest ROC curve areas were found for an N-terminal fragment of complement C3c chain (m/z 28 119) and an internal fragment of fibrinogen -E chain (m/z 5908). Immunoglobulin light chain (m/z 24 505) positively correlated with the viral load.

Conclusions: Specific proteomic fingerprints present in the sera of adult SARS patients could be used to identify SARS cases early during onset with high specificity and sensitivity.