gms | German Medical Science

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

08. - 11.05.2004, Lübeck

Article

Send article

Immune responses in patients with SARS: Lessons from cytokine and gene expression profiling, FACS analysis and epitope mapping

Talk

Search Medline for

  • Mark J. Cameron - University Health Network, Toronto, ON, Canada
  • Luoling Xu - University Health Network, Toronto, ON, Canada
  • Longsi Ran - University Health Network, Toronto, ON, Canada
  • Cheryl 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
  • Canadian SARS Research Network (CSRN)
  • corresponding author presenting/speaker 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. Doc04sars12.04

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/sars2004/04sars059.shtml

Published: May 26, 2004

© 2004 Cameron 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

Text

Severe acute respiratory syndrome (SARS) emerged in late 2002 and infected over 8400 persons worldwide to date with an accompanying case fatality rate of approximately 11%. A novel coronavirus (CoV), causing a spectrum of disease ranging from non-specific flu-like symptoms and lung inflammation to severe respiratory distress requiring intensive care, has been identified as the etiologic agent of SARS. While the SARS CoV epidemic of 2003 was largely contained through public health measures, it is unknown whether or not human SARS CoV will cause another global outbreak.

To better understand the involvement of the immune system in the severity and pathology of SARS, we have conducted a series on experiments. We have analyzed plasma and RNA from blood samples collected longitudinally from over 60 SARS patients (including 9 ICU patients) during the prodrome, acute and convalescent phases of the disease for cytokine and gene expression profiles. We have also examined leukocyte subset composition in peripheral blood from acute and convalescent SARS patients. Furthermore, gene expression profiling has been performed on lungs from autopsied specimens. Finally, we performed T cell epitope mapping against SARS CoV antigens.

We have found that within 48 hours of onset of SARS symptoms, CXCL10 and IFN-gamma are abundantly upregulated at the protein and RNA levels. Initial stages of the disease are also characterized by a drop in T cells and monocytes. Gene expression profiles in PBMCs from SARS patients indicate that early interferon responses are generated that can persist in persons who suffer a protracted illness. Lungs from autopsied individuals display ongoing immune responses rich in activated T cell markers. Our epitope mapping experiments, design to define T cell responses in SARS patients, have distinguished deviations in adaptive immune responses between patients with a good prognosis versus those with a poor outcome. Overall, we propose a model of lung injury in SARS patients that is a consequence of unabated adaptive immune responses leading to organ failure.

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