HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

TY - JOUR

T1 - HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

AU - Busch, Robert

AU - Kollnberger, Simon

AU - Mellins, Elizabeth D

N1 - Draft accepted for publication. Review article, so not REF eligible.

PY - 2019/5/15

Y1 - 2019/5/15

N2 - Our understanding of the mechanisms underlying HLA associations with inflammatory arthritis continues to evolve. Disease associations have been refined, and interactions of HLA 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 HLA molecules, as well as general features of HLA associations with disease. We summarise evidence for various peptide-dependent and peptide-independent mechanisms by which HLA alleles might contribute to the pathogenesis of three types of inflammatory arthritis, rheumatoid arthritis, spondyloarthritis and systemic juvenile idiopathic arthritis. Also discussed are HLA allelic associations that shed light on the genetic heterogeneity of inflammatory arthritides and on the relationships between adult and pediatric forms of arthritis. Clinical implications range from improved diagnosis and outcome prediction to the possibility of using HLA associations in developing personalized strategies for the treatment and prevention of these diseases.© 2019, Springer Nature. The attached document (embargoed until 15/11/2019) is an author produced version of a paper published in NATURE REVIEWS RHEUMATOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

AB - Our understanding of the mechanisms underlying HLA associations with inflammatory arthritis continues to evolve. Disease associations have been refined, and interactions of HLA 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 HLA molecules, as well as general features of HLA associations with disease. We summarise evidence for various peptide-dependent and peptide-independent mechanisms by which HLA alleles might contribute to the pathogenesis of three types of inflammatory arthritis, rheumatoid arthritis, spondyloarthritis and systemic juvenile idiopathic arthritis. Also discussed are HLA allelic associations that shed light on the genetic heterogeneity of inflammatory arthritides and on the relationships between adult and pediatric forms of arthritis. Clinical implications range from improved diagnosis and outcome prediction to the possibility of using HLA associations in developing personalized strategies for the treatment and prevention of these diseases.© 2019, Springer Nature. The attached document (embargoed until 15/11/2019) is an author produced version of a paper published in NATURE REVIEWS RHEUMATOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

U2 - 10.1038/s41584-019-0219-5

DO - 10.1038/s41584-019-0219-5

M3 - Article

SN - 1759-4804

VL - 15

SP - 364

EP - 381

JO - Nature Reviews Rheumatology

JF - Nature Reviews Rheumatology

IS - June 2019

ER -