Human Leukocyte Antigens as Determinants of Drug-Specific Immune Responses and Genetic Risk Factors for SCARs

Abstract

Background: Research efforts have been concentrated to develop new biomarkers with a particular interest in cytokines and chemokines released from activated T cells. Studies on cytokine measurements after clinical drug challenge in  SCARS patients have reported an initial increase in serum TNF-α and IL-8 followed by elevation in IFN-γ, IL-6 and IL-10 levels. Early studies suggesting a weak association between some HLA serotypes and SJS/TEN. But later on  a strong connection between HLA alleles and drug-induced cutaneous reactions has been identified in numerous studies. It is of note that the HLA encoding genes are the most polymorphic of the whole human genome, and the distribution of the various alleles is quite heterogeneous across human populations from different geographic locations. This makes necessary specific studies on defined ethnic groups and hinders the identification of strongly associated HLA alleles in populations with high rates of genetic exchange resulting from migration, such as the populations of Europe and North America. In this regard, it is interesting that the prognostic value of HLA-B*57:01 as a risk factor to develop abacavir hypersensitivity was initially questioned after reports of low sensitivity in some population groups such as Hispanic patients and those of African descent. However, further studies showed a strong association for patch test-confirmed cases across all ethnicities.