The efforts of numerous investigators during the past three decades have resulted in the recognition of a major histocompatibility complex (MHC) in humans consisting of the alleles of at least seven closely linked loci on the short arm of autosomal chromosome 6. The antigens that the genes of this region code for were first detected on white blood cells and were therefore originally referred to as human leukocyte antigens (HLA). Initially, these antigens interested primarily transplantation physicians, as similarity between donor and recipient seemed to influence allograft survival; soon, however, it was recognized that certain clinical conditions might be associated with one or more antigens of this system. A large number of diseases have been studied, and individual or combinations of antigens have appeared with greater frequency than would be expected in the normal population. This increase is particularly true for rheumatic diseases and related syndromes with features of altered immunoreactivity, where, as will be discussed, the strongest and most significant associations have been demonstrated. Although it is recognized that many of the rheumatic disease may occur as a result of multiple genetic factors, the strongest influences have been with the HLA genes of the MHC. This chapter reviews the basic concepts of immunogenetics, emphasizing the potential significance of the HLA system antigens in clinical rheumatology.
Gene. Segment of DNA that directs the synthesis of a polypeptide chain or protein.
Allele. Alternative form of the same gene, resulting from mutation or duplication.
Locus. The position of a gene on any given chromosome.
Genotype. The genetic composition of an individual.
Phenotype. The observed expression of the genotype.
Haplotype. Closely linked loci, transmitted as a unit from each parent; two haplotypes constitute the genotype.
Allo-antigen. Product of the A, B, C, or DR, DP, or DQ loci