Figure 2

HLA-allele association and p-i concept. Some drugs elicit severe, often CD8-dominated, immune reactions in patients with a certain HLA-B alleles (carbamazepine and HLA-B*1502, allopurinol with HLA-B*5801, abacavir with HLA-B*5701). If these drugs stimulate via the p-i concept (as well documented for carbamazepine [CBZ], but not abacavir or allopurinol), then the strong HLA association would be explained by the ability of only the selected HLA allele to supplement the activation caused by the respective drug. In the example given, the HLA alleles B*0701 or B*2701 would be unable to supplement this initial signal by CBZ. However, none of the existing hypotheses can explain the finding that some of these alleles are found to be involved only in certain human races (eg, CBZ and HLA-B*1502 in Han Chinese). SJS indicates Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.