HLA-B-HLA-C LINKAGES IN 2000+ VOLUNTEER BONE MARROW DONORS

HLA-B-HLA-C LINKAGES IN 2000+ VOLUNTEER BONE MARROW DONORS
A-M Little, S Cleaver, R Holman, H Ogilvy, J O’Shea, F Tavarozzi, SGE Marsh and JA Madrigal, The Anthony Nolan Bone Marrow Trust, London, UK

HLA-C molecules function in both T cell and NK cell mediated immune responses. Additionally, polymorphism within HLA-C heavy chains may contribute to indirect antigen presentation. With improvements in DNA based methodologies for HLA-C typing and the role of HLA-C matching in bone marrow transplantation being more evident, more transplant centres are increasingly including HLA-C locus typing in their bone marrrow donor/recipient matching programs.
Between the period 1996 to 1999, over 2153 potential or actual bone marrow donors from the ANBMT Register were HLA-C typed by SSP methods. This predominantly caucasoid population was also typed for HLA-A and -B by serology and/or DNA based methods. Probable HLA-B-HLA-C haplotypes were analysed. Of the 4306 haplotypes, 110 were considered ambiguous and not considered further e.g. B44, B62; Cw*04, Cw*16. The remaining haplotypes were divided into 34 groups based on HLA-B type. For some HLA-B allotypes, 99-100% association with one HLA-C type was found (e.g. B49-Cw*07, 100%, n=52 and B8-Cw*07, 99%, n=514), whereas for others there were clearly numerous different HLA-C types associated with HLA-B type e.g. for B44 (n=881): Cw*0501 47.2%, Cw*16 36.5%, Cw*04 6.4%, Cw*07 7.6% and Cw*0202, 1.5%, with the remaining rarer haplotypes constituting 0.8%. This observation of multiple associations such as with B44 is likely but not exclusively a reflection of allelic variation within the HLA-B44 group, with high resolution analysis showing association between B*44 alleles with particular Cw* alleles e.g. B*4405-Cw*0202.
The results from this analysis support previous reports on HLA-B-HLA-C associations1 and in addition, as more samples have been analysed, we can report on more infrequent associations. This data supports the requirement for HLA-C typing of bone marrow donors and patients, even for those HLA-B alleles which are strongly associated with only one HLA-C type.
1Bunce et al. Tissue Antigens 48: 680 1996.