Genetic polymorphisms in genes controlling innate immunity as risk factors for childhood acute lymphoblastic leukaemia

控制先天免疫基因的遗传多态性是儿童急性淋巴细胞白血病的危险因素

• 批准号: nhmrc : 350908
• 负责人: Dr Lesley Ashton
• 金额: $ 16.1万
• 依托单位: The University of New South Wales
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/genetic-polymorphisms-genes-lymphoblastic-leukaemia/94576
• 关键词: Genetic; polymorphisms; genes; controlling; innate

For some time now, researchers have speculated that the development of childhood leukaemia is related to exposure to an infectious agent. However, a causal pathogen is yet to be identified. Recent studies have shown that the initial recognition of microbes as they enter the human body is determined by a group of receptors, toll-like receptors (TLRs), which selectively bind to essential components of these pathogens. This process allows the body to respond immediately to microbial invasion; a process which is vital during early childhood, when clonal expansion of antibodies and other host defences is inadequate. It is becoming increasingly apparent that this innate immune response is not just the first line of defence but a necessary event for the development of an adaptive immune response. We propose that the innate immune system of children carrying TLR gene variants may be less effective at detecting the presence of microbial pathogens in the environment. We hypothesize that by dampening the stimulation of innate immunity in early childhood, TLR gene variants may indirectly cause a dysfunction in the maturation of a child's immune system and increase the chance of a pre-leukaemic clone emerging, leading to the development of childhood leukaemia.

一段时间以来，研究人员推测儿童白血病的发生与接触传染性物质有关。然而，致病病原体尚未确定。最近的研究表明，当微生物进入人体时，它们的最初识别是由一组受体决定的，Toll样受体（TLR），它们选择性地结合这些病原体的基本成分。这一过程使身体能够立即对微生物入侵作出反应;这一过程在儿童早期至关重要，因为此时抗体和其他宿主防御的克隆扩增不足。越来越明显的是，这种先天免疫反应不仅是第一道防线，而且是适应性免疫反应发展的必要事件。我们认为，携带TLR基因变异的儿童的先天免疫系统在检测环境中微生物病原体的存在方面可能不太有效。我们推测，通过抑制儿童早期先天免疫的刺激，TLR基因变异可能间接导致儿童免疫系统成熟的功能障碍，并增加白血病前克隆出现的机会，导致儿童白血病的发展。