BackgroundSevere 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.ResultsThe 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.ConclusionsThis 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.

IntroductionFragment crystallizable receptors (FcRs) are receptors on immune cells that bind to the Fc region of immunoglobulins. Fc␥Rs that bind to the most common type of immunoglobulin (IgG), are expressed on the surface of many different immune cell types including monocytes, macrophages, dendritic cells, and neutrophils. [1][2][3] In humans, 3 different classes of activatory IgG receptors have been defined: Fc␥RI (CD64), Fc␥RIIa (CD32a), and Fc␥RIII (CD16), each of which has a variety of isoforms with differing affinities for IgG, tissue distribution, and level of expression. [1][2][3][4][5][6] The high affinity IgG receptor, Fc␥RI, is a 72-kD type-I membrane glycoprotein constitutively expressed on monocyte and macrophage lineage cells. 4 Fc␥RI is a member of the multichain immune recognition receptor family, comprising hetero-oligomeric complexes of a ligand-binding ␣-chain and a signaling ␥-chain usually found in association with other immune receptors. [1][2][3][4][5][6] The ␥-chain contains a signaling motif termed the "immunoreceptor tyrosinebased activation motif" (ITAM): it is through the ITAM-bearing chain that most FcRs trigger intracellular signal transduction cascades. The low-affinity receptor, Fc␥RIIa, is the most broadly distributed human Fc␥R and is expressed on many cell types, such as monocytes, neutrophils, and platelets. 1,7 This low-affinity receptor preferentially binds complexes of IgG and is the only Fc receptor that contains an ITAM of its own. Thus, it is the only Fc receptor that does not need to oligomerize with a ␥-chain in order to signal. 4,8,9 There is no identified murine equivalent of Fc␥RIIa. 1 On myeloid cells, aggregation of Fc␥Rs during the early stages of infection leads to several cellular responses, including the internalization of immune complexes by endocytosis or opsonized particles through phagocytosis, degranulation with the release of proteases, activation of respiratory burst, and secretion of cytokines. 5,[10][11][12] The presentation of antigens derived from internalized complexes forms an important component of our adaptive immune response, and dysregulation of this pathway is reported to be linked to increased susceptibility to bacterial sepsis. 13 The safe clearance of immune complexes toward the latter stages of infection is also dependent on FcR expressing mononuclear phagocytes. Dysfunction in the clearance of immune complexes is reported to be associated with immunopathology, autoimmunity, and allergic disease. 9,14 This represents one of the critical but poorly understood functions of Fc receptors, ie, the determination of the antigenic fate of immune complexes; specifically, whether to internalize and digest them in a way that is noninflammatory or to reinforce antigen presentation combined with immune activation and associated proinflammatory signaling.Studies on differential functions mediated by individual Fc receptors in immune activation/homeostasis are complicated by the coexistence of several FcRs on phagocytic cells-it is difficult to identi...

Background: Mast cells are well established effectors of IgE-triggered allergic reactions and immune responses to parasitic infections. Recent studies indicate that mast cells may play roles in adaptive and innate immunity, suggesting an innovative view of the regulation of immune responses. Here, we profiled the transcriptome of human mast cells sensitized with IgE alone, or stimulated by FcεRI aggregation.

Multiple myeloma is the abnormal clonal expansion of post germinal B cells in the bone marrow. It was previously reported that clonogenic myeloma cells are CD138−. Human MM cell lines RPMI8226 and NCI H929 contained 2-5% of CD138− population. In this study, we showed that CD138− cells have increased ALDH1 activity, a hallmark of normal and neoplastic stem cells. CD138−ALDH+ cells were more clonogenic than CD138+ALDH− cells and only CD138− cells differentiated into CD138+ population. In vivo tumor initiation and clonogenic potentials of the CD138− population was confirmed using NOG mice. We derived a gene expression signature from functionally validated and enriched CD138− clonogenic population from MM cell lines and validated these in patient samples. This data showed that CD138− cells had an enriched expression of genes that are expressed in normal and malignant stem cells. Differentially expressed genes included components of the polycomb repressor complex (PRC) and their targets. Inhibition of PRC by DZNep showed differential effect on CD138− and CD138+ populations. The ‘stemness’ signature derived from clonogenic CD138− cells overlap significantly with signatures of common progenitor cells, hematopoietic stem cells, and Leukemic stem cells and is associated with poorer survival in different clinical datasets.

We performed gene expression profiling in Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoproliferative disorder in children and young adults (TNKLPDC) in order to understand the molecular pathways deregulated in this disease and compared it with nasal-type NK/T-cell lymphoma (NKTL). The molecular and phenotypic signature of TNKLPDC is similar to NKTL, with overexpression of p53, survivin and EZH2. Down-regulation of EZH2 in TNKLPDC cell lines led to an increase in apoptosis and decrease in tumor viability, suggesting that EZH2 may be important for the survival of TNKLPDC cells and hence potentially a useful therapeutic target. Notably, our gene expression profiling revealed a distinctive enrichment of stem cell related genes in TNKLPDC compared to NKTL. This was validated by a significantly higher expression of aldehyde dehydrogenase 1 (ALDH1) in TNKLPDC cell lines compared to NKTL cell lines. The novel discovery of cancer stem cell properties in TNKLPDC has potential therapeutic implications in this group of disorders.