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We report a discordance between complement-dependent cytotoxicity and next-generation sequencing molecular typing revealing HLA-B*15:47:01 allele with undefined serological equivalent confirmed by high-level immunization against the B15 serotype. Due to the high-level immunization against HLA-B15 and B70 antigens, we considered the HLA-B*15:47:01 allele to be B Blank and not as B15 or B70 serological specificity., (© 2019 John Wiley & Sons Ltd.)

The human leucocyte antigen (HLA) system is well known for its association with certain diseases such as ankylosing spondylitis, celiac disease and many others. More recently, severe and even fatal drug hypersensitivity reactions linked to particular HLA alleles have been discovered. The significance of these discoveries has led the European Medicines Agency (EMA) and its member state agencies to recommend HLA gene testing before initiation of drug treatment. To date, the following drugs have been identified as causing significant drug hypersensitivity reactions in patients who have the following HLA alleles: abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02/A*31:01 and finally allopurinol and HLA-B*58:01. This review will outline and discuss these three drugs and their associated HLA alleles as well as examine the pathogenesis of the drug hypersensitivity reactions., (© 2011 Blackwell Publishing Ltd.)

Using PCR with sequence-specific primers (SSP) and subsequent sequencing of exons 2 and 3, we identified an example of B*15:33 in a likely north-western European Caucasoid volunteer haemopoietic stem cell (HSC) donor. This was only the second example submitted to the IMGT/HLA database since B*15:33 was first described in 1996. B*15:33 differs from B*15:01:01:01 by three nucleotides resulting in two amino acid differences with B*15:01 (131S>R, 138T>K). This allele encodes a typical HLA-B62 specificity--as confirmed using 17 local antisera from parous women and 19 monoclonal antibodies directed towards B15, B62 and B63 specificities. Importantly, it also reacted as a Cw5/Cw8 specificity when tested against 21 Cw5, Cw5/Cw8 and Cw8 antisera. This Cw5/Cw8 reactivity is probably due to the B*15:33 specificity having lysine at position 138 which is possessed by numerous C*05 and many C*08 products. B*15:33 is likely to have derived from a HLA-B/C inter-locus gene conversion event. HLA-B*15:33 is clearly rare--this single example was found during the HLA PCR-SSP-based typing of 57,079 potential HSC donors. This indicates an allele frequency of <0.00001 in blood donors resident in Wales. An Epstein-Barr virus transformed B-cell line from the HLA-B*15:33 donor is available., (© 2011 Blackwell Publishing Ltd.)