基因差异性表达及易感性在急性风湿热疾病的细胞毒性、趋化及凋亡中起一定作用

Abstract

It is unknown why only some individuals are susceptible to acute rheumatic fever (ARF). We investigated whether t*8-9 here are differences in the immune response, detectable by gene -, between individuals who are susceptible to ARF and those who are not. Peripheral blood mononuclear cells (PBMCs) from 15 ARF-susceptible and 10 nonsusceptible (control) adults were stimulated with rheumatogenic (Rh+) group A streptococci (GAS) or nonrheumatogenic (Rh-) GAS. RNA from stimulated PBMCs from each subject was cohybridized with RNA from unstimulated PBMCs on oligonucleotide arrays to compare gene -. Thirty-four genes were significantly differentially expressed between ARF-susceptible and control groups after stimulation with Rh+ GAS. A total of 982 genes were differentially expressed between Rh+ GAS- and Rh- GAS-stimulated samples from ARF-susceptible individuals. Thirteen genes were differentially expressed in the same direction (predominantly decreased) between the two study groups and between the two stimulation conditions, giving a strong indication of their involvement. Seven of these were immune response genes involved in cytotoxicity, chemotaxis, and apoptosis. There was variability in the degree of - change between individuals. The high proportion of differentially expressed apoptotic and immune response genes supports the current model of autoimmune and cytokine dysregulation in ARF. This study also raises the possibility that a "failed" immune response, involving decreased - of cytotoxic and apoptotic genes, contributes to the immunopathogenesis of ARF.

摘要

基因差异性表达及易感性参与了急性风湿热(ARF)细胞毒性，细胞趋化和细胞凋亡作用。目前对于某些人群易患ARF原因尚不明确。探讨ARF易感人群和正常人群中的免疫反应和基因表达是否具有个体差异性。采集15例易感者和10例非易感对照者的外周血单核细胞(PBMC)，随后将其进行Rh(+)或Rh(-)的A型溶血性链球菌(GAS)转染并进行培养。从转染和未转染的PBMCs中提取RNA，并进行杂交反应，我们以寡核苷酸为单位对两组基因表型进行比较。发现Rh (+) GAS转染后的敏感组与对照组有34个基因明显不同。在Rh(+)GAS和Rh(-)GAS转染的易感组之间共有982个基因明显不同，在转染的与未转染两组发现有13个基因明显表达不同，提示这些基因在发病中起一定的作用，其中7个是免疫基因，参与细胞毒性，趋化和凋亡作用。这些基因具有个体表达差异。不同比例的细胞凋亡和免疫反应基因支持了ARF的自身免疫反应和细胞因子失调的假说。这项研究提示，抑制免疫反应可能会减少细胞毒性和凋亡基因的表达，也解释了ARF的免疫病理机制。

引自：Susceptibility to acute rheumatic Fever -d on differential - of

genes involved in cytotoxicity, chemotaxis, and apoptosis. Infect Immun.2014 Feb;82(2):753-61

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