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

一段时间以来，研究人员推测儿童白血病的发展与接触传染性病原体有关。然而，病因病原体尚未确定。最近的研究表明，微生物进入人体后的最初识别是由一组受体决定的，toll样受体（TLRs），它们选择性地结合这些病原体的基本成分。这个过程使身体能够立即对微生物入侵作出反应；在儿童早期，当抗体克隆扩增和其他宿主防御不足时，这一过程至关重要。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。我们假设，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，增加白血病前克隆出现的机会，从而导致儿童白血病的发展。

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.