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International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

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Proinflammatory gene expression profiles and severity of disease course in SARS patients

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  • corresponding author presenting/speaker Luoling Xu - University Health Network, Toronto, ON, Canada
  • Longsi Ran - University Health Network, Toronto, ON, Canada
  • Mark J. Cameron - University Health Network, Toronto, ON, Canada
  • Des Persad - University Health Network, Toronto, ON, Canada
  • Ali Danesh - University Health Network, Toronto, ON, Canada
  • Wayne Gold - University Health Network, Toronto, ON, Canada
  • Shaf Keshavjee - University Health Network, Toronto, ON, Canada
  • James Brunton - University Health Network, Toronto, ON, Canada
  • Mark Loeb - McMaster University, Hamilton, ON, Canada
  • the Canadian SARS Research Network
  • David J. Kelvin - University Health Network, Toronto, ON, Canada

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sarsP12.02

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/sars2004/04sars135.shtml

Published: May 26, 2004

© 2004 Xu et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Severe acute respiratory syndrome (SARS) is a highly contagious disease that causes a spectrum of symptoms in humans ranging from non-specific flu-like presentations and lung inflammation to severe respiratory distress requiring intensive care. The molecular and genetic determinants that lead to poor outcome in some SARS patients are presently unclear; however the highly variable clinical course and severity of SARS CoV infection may be partially determined by the immune system.

To better understand how host immune responses develop in SARS patients, our strategy was to isolate RNA from peripheral blood samples collected longitudinally from patients of different SARS severity and disease course and analyse gene expression profiles by cDNA microarray with emphasis on immunological parameters. We analysed samples from over 60 SARS patients (including 9 ICU patients) during the prodrome, acute and convalescent phases of the disease. We also isolated RNA from 25 suspect SARS cases (non-SARS) and 12 healthy controls.

Our hierarchical cluster analyses of more than 175 gene expression datasets revealed significant roles for interferon (IFN) response gene families in controlling immune responses against SARS CoV. Moreover, a critical period of in the disease course of SARS when patients either regained health or worsened patterns was hallmarked by expression of IFN-gamma-induced genes, proinflammatory mediators and stress proteins. Lastly, we discovered that class prediction software could accurately discriminate genetic differences and accurately segregate SARS patients on the basis of the severity of their disease course and outcome.

Understanding the networks of genes that dictate the clinical course of SARS may facilitate the identification of prognostic biomarkers and the tailoring of specific immunotherapies for SARS patients.

Funding for this work was provided by the Canadian Institutes of Health Research, the Canadian Network for Vaccines and Immunotherapies (CANVAC) and Genome Canada.