Human leukocyte antigen (HLA) DR4 occurs in about 70% of patients with rheumatoid ahritis HLA DR4 encoded in the major histocompatibility complex (MHC) region on
Rheumatoid ahritis (RA) is a common form of inflammatory ahritis, occurring throughout the world and in all ethnic groups. The prevalence of RA is approximately 0.8-1.0% in Europe and the Indian subcontinent, with a female-to-male ratio of 3 : 1. The prevalence is lower in South-east Asia (0.4%). The highest prevalence in the world is in Pima Indians (5%). It is a chronic disease characterised by a clinical course of exacerbations and remissions . RA is a complex disease with both genetic and environmental components. The impoance of genetic factors is demonstrated by higher concordance of RA in monozygotic (12-15%) compared with dizygotic twins (3%), and an increased frequency of disease in first-degree relatives of patients. Genome-wide association studies have detected nearly 100 loci that are associated with the risk of developing RA. The strongest association is with variants in the HLA region. Recent studies have shown that the association with HLA is determined by variations in three amino acids in the HLA-DRb1 molecule (positions 11, 71 and 74) and single variants HLA-B (at position 9) and HLA-DPb1 (at position . The HLA locus is located on the sho arm of chromosome 6 and covers a 7.6 Mb region that contains over 250 highly polymorphic genes. The region is organized in three sub-regions: class I, class II and class III, which all have different functions. Both class I and II regions encode for glycoproteins that are expressed as cell surface receptors, whereas the class III region contains genes that encode for a variety of secreted immune system proteins, including complement factors and cytokines. The class I region encodes for three main subsets of HLA molecules; HLA-A, HLA-B and HLA-C. Class I HLA molecules are composed of an HLA-coded heavy a-chain and an invariant light chain, beta-2 microglobulin (b2m), which is essential for functional expression of the HLA molecule at the cell surface. The a-chain is folded to form a peptide-binding cleft that is "closed" and can accommodate sho antigenic peptides, typically 8-10 amino acids long. These class I molecules are expressed on all nucleated cells and specialize in presentation of intracellular antigens, including viral antigens, to cytotoxic (CD8+) T cells. Genes in the class II region encode for HLA-DR, HLA-DP and HLA-DQ molecules as well as a few other related proteins. Class II HLA molecules are composed of an a-chain and a b-chain, both coded by the HLA class II region. Unlike the class I molecules, the peptide-binding cleft of class II molecules are "open" which allows the accommodation of larger peptides of 15-20 amino acids long. Class II molecules are initially expressed on the cell surface of immune cells, in paicular antigen presenting cells such as macrophages or dendritic cells, as well as B cells and activated T cells. These molecules present antigens from outside the cell to (CD4+) T cells which in turn stimulate B cells to produce antibodies towards that specific antigen. This results in an antigen specific immune response. After activation of the immune system, the HLA class II molecules can be expressed on other cells. Ref - pubmed.com , Davidsons 23e p1044
Chromosome 6
Chromsome 9
Chromosome 18
Choromosome 22
Immune system