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Sent to Peter Tsai-November 2003 Mtg
ABSTRACT
Presenter: Dr. David J. Kelvin
Title: Immune Responses in Paitents with Severe Acute Respiratory Syndrome
(SARS): Lessons from Cytokine and Gene expression Profiling, FACS Analysis, and
Epitope Mapping”
A novel coronavirus has been identified as the etiologic agent for severe acute respiratory
syndrome (SARS). Individuals infected with SARS present with fever, cough and
myalgia that may progress to lung inflammation including acute respiratory distress
syndrome. We analyzed tissue and blood samples collected longitudinally from suspect
or probable SARS patients during the prodrome, acute phase of SARS and convalescence
for the expression of CXCL10. As controls we collected samples from healthy
individuals, suspect SARS cases and individuals that presented with SARS-like
symptoms. CXCL10 is an inflammatory chemokine that is induced by interferon
cytokines. It’s cognate receptor, CXCR3, is expressed on lymphocyte poplulations and
most highly expressed on memory and activated T cells. CXCL10 has been shown to be
critical in the defense against neurotropic coronavirus infection in animal models. There
was an overall increase in CXCL10 plasma levels in probable SARS patients compared
to non-SARS individuals as well as convalescent individuals. During the course of the
disease, plasma levels of CXCL10 decreased in patients that went on to recovery but
remained elevated in patients that died. Using real-time PCR, we also investigated the
expression of CXCL10 and CXCR3 in peripheral blood and lung autopsy tissue from
SARS patients. There was an increased expression of both CXCL10 and CXCR3 in both
peripheral blood and the lung tissues in comparison to controls. We hypothesize that the
maintenance of high CXCL10 expression in the lung in SARS patients may generate a
positive feedback loop resulting in the continual recruitment of activated T cells leading
to severe lung inflammation. CXCL10 may be a useful target for both diagnostic and
therapeutic modalities.