Jin Ping, Wang Ena
Immunogenetics Section - Department of Transfusion Medicine - Clinical Center - National Institutes of Health Bethesda, Maryland USA.
J Transl Med. 2003 Nov 18;1(1):8. doi: 10.1186/1479-5876-1-8.
The pathology of humans, in contrast to that of inbred laboratory animals faces the challenge of diversity addressed in genetic terms as polymorphism. Thus, unsurprisingly, treatment modalities that successfully can be applied to carefully-selected pre-clinical models only sporadically succeed in the clinical arena. Indeed, pre-fabricated experimental models purposefully avoid the basic essence of human pathology: the uncontrollable complexity of disease heterogeneity and the intrinsic diversity of human beings. Far from pontificating on this obvious point, this review presents emerging evidence that the study of complex system such as the cytokine network is further complicated by inter-individual differences dictated by increasingly recognized polymorphisms. Polymorphism appears widespread among genes of the immune system possibly resulting from an evolutionary adaptation of the organism facing an ever evolving environment. We will refer to this high variability of immune-related genes as immune polymorphism. In this review we will briefly highlight the possible clinical relevance of immune polymorphism and suggest a change in the approach to the study of human pathology, from the targeted study of individual systems to a broader view of the organism as a whole through immunogenetic profiling.
与近交系实验动物不同,人类病理学面临着以多态性的遗传学术语表述的多样性挑战。因此,成功应用于精心挑选的临床前模型的治疗方法仅偶尔能在临床领域取得成功,这并不奇怪。事实上,预制的实验模型有意回避了人类病理学的基本本质:疾病异质性的不可控复杂性和人类内在的多样性。本综述并非详述这一明显事实,而是呈现新出现的证据,即细胞因子网络等复杂系统的研究因日益被认识到的多态性所决定的个体差异而进一步复杂化。多态性在免疫系统基因中似乎广泛存在,这可能是生物体面对不断演变的环境进行进化适应的结果。我们将这种免疫相关基因的高变异性称为免疫多态性。在本综述中,我们将简要强调免疫多态性可能的临床相关性,并建议改变人类病理学的研究方法,从对单个系统的靶向研究转变为通过免疫遗传学分析对生物体整体进行更广泛的观察。