Can HLA-DRB4 be a susceptibility locus?
Since our first report on a HLA-DR53 association in leukaemia 14, we have been frequently asked why the susceptibility genotype is that of a class-II supertype but not a classical class-II genotype. There seems to be some scepticism about the association of DR53/DRB4 with leukaemia. The HLA-DRB4 locus is one of the MHC class-II loci. As a structurally separate gene and similar to three other HLA-DRB genes, it is expressed, except when it is on some DR7 haplotypes, albeit at a lower level than classical DRB1 alleles. Although it is a difficult antigen to be picked up by standard serology, there are monoclonal antibodies that recognize the HLA-DR53 antigen. One of them, 109d6, is specific for the HVR3-encoded epitope, and positivity for this epitope is associated with a very high risk (RR = 7.88; P < 0.000005) for adult AML 13. Interestingly, this epitope is mimicked by a number of carcinogenic / leukaemogenic viruses in its entirety, i.e., up to seven out of seven consecutive amino acid
