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. 2005 Jan 18:6:2.
doi: 10.1186/1471-2172-6-2.

Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

Renji Reghunathan  1 , Manikandan Jayapal, Li-Yang Hsu, Hiok-Hee Chng, Dessmon Tai, Bernard P Leung, Alirio J Melendez
Affiliations

Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome

Renji Reghunathan et al. BMC Immunol. .

Abstract

Background: Severe acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls.

Results: The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis.

Conclusions: This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.

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Figures

Figure 1
Figure 1
Clustering and distribution of differentially expressed genes. A. Hierarchical clustering of gene expression data from PBMCs from 10 SARS patients showing different classes of gene expression profiles. Each row represents a separate gene and each column a separate SARS patient. 248 genes have been selected for this analysis which is described in methods. The expression index for each gene (rows) in each sample (column) is indicated by a color code. The color scale ranges from saturated green for log ratios -3.0 and above to saturated red for log ratios 3.0 and above. Red indicates increased gene expression levels, whereas green indicates decreased levels compared with normal samples. B. Pie chart showing the percentage distribution of the differentially expressed genes from the PBMCs of 10 SARS patients.
Figure 2
Figure 2
Real-Time PCR of selected genes. PBMCs were isolated from 4 healthy volunteers (Control), from 10 SARS infected patients (SARS), and from 5 influenza virus infected patients (Influenza). Total RNA was extracted from all the samples and Light-Cycler Real-Time PCR was performed. The concentrations of these genes mRNA were calculated using respective standard curves. Lactoferrin expression (LTF); Lipocalin expression (Lipocalin); S100P expression (S100P); FCGR3A expression (FCGR3A); TLR2 expression (TLR2); Interferon Alpha expression (IFNa); Interferon Beta expression (IFNb); Interleukin 12-p40 expression (IL-12); Tumor Necrosis Factor Alpha expression (TNFa); and GAPDH expression (GAPDH). Results are expressed as average ± SD of gene expression for each group (control n = 4; SARS n = 10; and influenza n = 5).
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