HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

Our understanding of the mechanisms underlying HL A associations with inflammatory arthritis continues to evolve. Disease associations have been refined, and interactions of HL A genotype with other genes and environmental risk factors in determining disease risk have been identified. This Review provides basic information on the genetics and molecular function of HL A molecules, as well as general features of HL A associations with disease. Evidence is discussed regarding the various peptide-dependent and peptide-independent mechanisms by which HL A alleles might contribute to the pathogenesis of three types of inflammatory arthritis: rheumatoid arthritis, spondyloarthritis and systemic juvenile idiopathic arthritis. Also discussed are HL A allelic associations that shed light on the genetic heterogeneity of inflammatory arthritides and on the relationships between adult and paediatric forms of arthritis. Clinical implications range from improved diagnosis and outcome prediction to the possibility of using HL A associations in developing personalized strategies for the treatment and prevention of these diseases.