Study requirements for investigating HLA-associated progression of HIV disease, and review.

Abstract

Human Leukocyte Antigens (HLA), also known as transplantation antigens, determine the immune response. We give a brief account of them, and of more complex immunology, to explain why HLA phenotype may be specifically important in HIV disease, as it is in other infectious diseases.1 Study requirements for investigating HLA-associated progression of HIV disease are illustrated with Scottish data; susceptibility to HIV infection is considered only briefly. Systematic review of published and other diverse data on three HLA associations with HIV progression is attempted, and the difficulties illustrated, for: the ancestral phenotype HLA-A1, B8, DR3 (which is associated with a range of autoimmune diseases); the allele B35 (which is common in Africans, and has been implicated empirically in HIV progression); and B27 (because Ohno2 established a theoretical basis for its association with slow HIV progression, which McNeil et al. 3 corroborated). The systematic review suggests that major HLA effects on HIV progression are equivalent to at least 20 additional years of age. We also present a partial validation of Kaslow's HLA profile score4 which models intermediate effects also, but conclude that more rigorous analysis still requires an international multi-cohort analysis workshop to be convened to map HLA effects on HIV disease progression.5,,6 The most studied genes of the major histocompatibility complex (MHC) encode for the polymorphic Human Leukocyte Antigens (HLA). These are molecules on the surface of nucleated cells which represent the major mechanism by which the T lymphocyte immune system recognizes what is \`self' from \`non-self'. There are three classes of MHC genes: class I, encoding HLA-A, B and C, which are found on all nucleated cells; class II, encoding HLA-DR, DP and DQ, which are located on immune cells, namely: B lymphocytes, activated T lymphocytes and macrophages; and class III, of which more …