Abstract
BackgroundThe underlying change of gene network expression of Guillain-Barré syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS.Methods and FindingsQuantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses.256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05). FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS.ConclusionsThis study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies.
Highlights
Guillain-Barresyndrome (GBS) is an inflammatory demyelinating disease of the peripheral nervous system that is characterized by acute areflexic paralysis [1]
These studies, carried out on body fluid analysis, did not provide critical information on the molecular modifications in the inflammatory cells. These studies did not reveal information about the changes of systemic signaling networks associated with GBS. We address both these questions by analyzing the global quantitative gene expression profile in peripheral blood leukocytes
Of 15 genes quantified by Real-time polymerase chain reaction (RT-PCR), 8 up-regulated genes (FOS, PTGS2, HMGB2, MMP9, LY96, TTRAP, ANXA3, CREB1) were in good agreement with the results of microarray (Table 2)
Summary
Guillain-Barresyndrome (GBS) is an inflammatory demyelinating disease of the peripheral nervous system that is characterized by acute areflexic paralysis [1]. A number of infectious agents, such as Campylobacter jejuni and Mycoplasma, are proposed to induce T cell-mediated immune process against myelin sheath proteins or gangliosides [7,8,9,10,11,12,13]. The activated T cells could induce the production of autoantibodies or recruit macrophages on the surface of myelin sheath or the node of Ranvier [14,15,16,17]. The mediators released by activated macrophages may cause destruction of myelin sheath or axons [18,19]. The underlying change of gene network expression of Guillain-Barresyndrome (GBS) remains elusive.
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