Acknowledgements Much of the original work described in this review was carried out in association with Professor R. L. Dawkins, whose contribution is acknowledged. We are grateful to Ms Denise Witt, who carried out the studies described in Table 4, and to Michelle Corp, Lisa Boogerd and Lisa Sharland for their excellent clerical assistance. This work has been supported by the Immunogenetics Research Foundation and the National Health and Medical Research Council of Australia. Patricia Price is a Senior Research Officer (NHMRC). Publication number 9801 of the Department of Clinical Immunology, Royal Perth Hospital.
The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases
Article first published online: 28 APR 2006
Volume 167, Issue 1, pages 257–274, February 1999
How to Cite
Price, P., Witt, C., Allock, R., Sayer, D., Garlepp, M., Kok, C. C., French, M., Mallal, S. and Christiansen, F. (1999), The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases. Immunological Reviews, 167: 257–274. doi: 10.1111/j.1600-065X.1999.tb01398.x
- Issue published online: 28 APR 2006
- Article first published online: 28 APR 2006
Summary: An individual's major histocompatibility complex (MHC) ancestral haplotype (AH) is the dearest single determinant of susceptibility to MHC associated immunopathological disease, as it defines the alleles carried at all loci in the MHC. However, the direct effects of any of the 150–200 genes that constitute the MHC are difficult to determine since recombination only occurs at defined hotspots. This review concerns the 8.1 AH (HLA-A1, C7, B8, C4AQ0, C4B1, DR3, DQ2), which is carried by most Caucasians with HLA-B8. It is associated with accelerated human immunodeficiency virus (HIV) disease, and susceptibility to insulin-dependent diabetes mellitns (IDDM), systemic lupus erythematosus, dermatitis herpetiformis, common variable immunodeficiency and IgA deficiency, myasthenia gravis and several other conditions. We have mapped susceptibility genes for HIV, IDDM and myasthenia gravis co the central MHC between HLA-B and the tumour necrosis factor or complement genes. Here we consider which of the remaining 8.1-associated diseases are more closely associated with HLA-DR3 and/or DQ2. Several candidate genes in the central MHC have the potential to modulate immune or inflammatory responses in an antigen-independent manner, as is seen in studies of cultured cells from healthy carriers of the 8.1 AH. Hence these genes may act as a common co-factor in the diverse immunopathological conditions associated with the 8.1 AH.