Personalized Medicine for HLA-associated Drug-hypersensitivity Reactions

Mandvi Bharadwaj; Patricia Illing; Lyudmila Kostenko


Personalized Medicine. 2010;7(5):495-516. 

In This Article

Other HLA-associated ADRs

Various other ADRs associated with particular HLA alleles are outlined in Table 1. The data on these associations are more limited and often quite dated, and therefore they have not been discussed in detail. For example, an association between levimisole-induced agranulocytosis and HLA-B27 was observed in 1977, but limited data has been accrued since this time.[97] During the 1980s associations between gold sodium thiomalate, and to some extent D-penicillamine, induced proteinuria were found with HLA-DRw3 and HLA-B8,[98] as were associations between oxicam and sulfonamide-induced SJS/TEN with HLA-A2and B12, and HLA-A29, B12 and DR7, respectively.[99,100] However, these have not been substantiated by much recent data or high-resolution typing, and in the cases of oxicam and sulfonamides alternative associations have been observed in recent years.[53,55] By contrast, data on the association between ximegalatran-induced elevations in alanine aminotransferase (an indication of liver disease or hepatitis) and the HLA-DRB1*07–HLA-DQ haplotype is limited as it is no longer clinically relevant owing to the discontinuation of ximegalatran usage.[101] Clozapine-induced agranulocytosis has been well known for almost 30 years and the susceptibility has been associated with particular HLA allotypes[102] in specific ethnic backgrounds. However, these associations are still ambiguous and need further investigation in larger populations.

Overall, although the current literature on HLA associations with drug hypersensitivities does highlight the importance of genetic background, it also emphasizes the importance of the precise phenotyping of hypersensitivities. Furthermore, in most cases HLA-typing accompanied by the analysis of a panel of risk factors may better identify candidates potentially at risk of a particular hypersensitivity, thus increasing the efficacy of predictive screening.