HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: clinchem.2005.054460v1 51/12/2333    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Tang, N. L.-S. Articles by Lam, C. W.-K. Search for Related Content PubMed PubMed Citation Articles by Tang, N. L.-S. Articles by Lam, C. W.-K. Related Collections Clinical Immunology

Early Enhanced Expression of Interferon-Inducible Protein-10 (CXCL-10) and Other Chemokines Predicts Adverse Outcome in Severe Acute Respiratory Syndrome

Departments of¹ Chemical Pathology, ² Microbiology, ³ Anatomical and Cellular Pathology, and ⁴ Medicine and Therapeutics, Faculty of Medicine, and ⁵ Centre for Emerging Infectious Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.

^aAddress correspondence to this author at: Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, SAR, China. Fax 852-2632-2320; e-mail nelsontang{at}cuhk.edu.hk.

Background: Exaggerated activation of cytokines/chemokines has been proposed as a factor in adverse outcome of severe acute respiratory syndrome (SARS). Previous studies on chemokines have included only small numbers of patients, and the utility of plasma chemokines as prognostic indicators is unclear.

Methods: We studied 255 archival plasma samples collected during the first or second week after disease onset. The chemokines interferon-inducible protein-10 (IP-10), monokine induced by interferon- (MIG), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation normal T cell expressed and secreted (RANTES) were measured by cytometric bead array with a 4-color FACSCalibur flow cytometer. Reverse transcription and real-time quantitative PCR and immunohistochemical staining were performed to analyze the production of IP-10 in lung tissue at autopsy. Conditional logistic regression was used to identify independent predictors for adverse disease outcome.

Results: Increases in IP-10, MIG, and IL-8 during the first week after onset of fever were associated with adverse outcome (intensive care unit admission or death) in the univariate analysis. During the second week, only MIG concentration was associated with prognosis. After adjusting for other risk factors, plasma IP-10 concentration at the first week remained as an independent prognostic factor, with an odds ratio for adverse outcome of 1.52 (95% confidence interval, 1.05–2.55) per fold increase in plasma IP-10 concentration above the median. During the second week, chemokines provided little independent prognostic information. IP-10 was increased in lung tissue from patients who died of SARS.

Conclusions: Increased plasma IP-10 during the first week of SARS symptoms is an independent predictor of outcome. Chemokine activation may be an early event in SARS, and an exaggerated host response may produce complications.

The following articles in journals at HighWire Press have cited this article:

				H Li, N L-S Tang, P K-S Chan, C-Y Wang, D S-C Hui, C Luk, R Kwok, W Huang, J J-Y Sung, Q-P Kong, et al. Polymorphisms in the C-type lectin genes cluster in chromosome 19 and predisposition to severe acute respiratory syndrome coronavirus (SARS-CoV) infection J. Med. Genet., November 1, 2008; 45(11): 752 - 758. [Abstract] [Full Text] [PDF]

				V. C. C. Cheng, S. K. P. Lau, P. C. Y. Woo, and K. Y. Yuen Severe Acute Respiratory Syndrome Coronavirus as an Agent of Emerging and Reemerging Infection Clin. Microbiol. Rev., October 1, 2007; 20(4): 660 - 694. [Abstract] [Full Text] [PDF]

				M. J. Cameron, L. Ran, L. Xu, A. Danesh, J. F. Bermejo-Martin, C. M. Cameron, M. P. Muller, W. L. Gold, S. E. Richardson, S. M. Poutanen, et al. Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory Syndrome J. Virol., August 15, 2007; 81(16): 8692 - 8706. [Abstract] [Full Text] [PDF]

				J. Gu and C. Korteweg Pathology and Pathogenesis of Severe Acute Respiratory Syndrome Am. J. Pathol., April 1, 2007; 170(4): 1136 - 1147. [Abstract] [Full Text] [PDF]

				C.-T. K. Tseng, C. Huang, P. Newman, N. Wang, K. Narayanan, D. M. Watts, S. Makino, M. M. Packard, S. R. Zaki, T.-s. Chan, et al. Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor J. Virol., February 1, 2007; 81(3): 1162 - 1173. [Abstract] [Full Text] [PDF]

				P. B. McCray Jr., L. Pewe, C. Wohlford-Lenane, M. Hickey, L. Manzel, L. Shi, J. Netland, H. P. Jia, C. Halabi, C. D. Sigmund, et al. Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus J. Virol., January 15, 2007; 81(2): 813 - 821. [Abstract] [Full Text] [PDF]