Polymorphism in clinical immunology - From HLA typing to immunogenetic profiling

Abstract

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.

Figure 1

Increase in HLA-A*02 alleles during the last few years.

Figure 2

Increase in HLA-A, -B and -Cw alleles in the last few years.

Figure 3

Number of known polymorphism(s) of cytokines that occur in known regulatory regions, untranslated gene regions and coding regions. In coding regions only those polymorphisms that result in a chance in protein sequence are counted. The information was compiled to searches based on the following web-sites: ;

Figure 4

Number of polymorphism(s) occurring in selected genes associated with control of the innate immune response.