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Implications of juvenile idiopathic arthritis genetic risk variants for disease pathogenesis and classification

Nigrovic, Peter A.a,b; Martínez-Bonet, Martaa,d; Thompson, Susan D.c

doi: 10.1097/BOR.0000000000000637

Purpose of review We assess the implications of recent advances in the genetics of juvenile idiopathic arthritis (JIA) for the evolving understanding of inflammatory arthritis in children.

Recent findings JIA exhibits prominent genetic associations with the human leukocyte antigen (HLA) region, extending perhaps surprisingly even to the hyperinflammatory systemic JIA category. Some HLA associations resemble those for adult-onset inflammatory arthritides, providing evidence for pathogenic continuity across the age spectrum. Genome-wide association studies have defined an increasing number of JIA-linked non-HLA loci, many again shared with adult-onset arthritis. As most risk loci contain only noncoding variants, new experimental methods such as SNP-seq and innovative big-data strategies help identify responsible causative mutations, termed functional SNPs (fSNPs). Alternately, gene hunting in multiplex families implicates new genes in monogenic childhood arthritis, including MYD88 and the intriguing innate immune gene LACC1.

Summary Genetic data indicate a continuity between JIA and adult arthritis poorly reflected in current nomenclature. Advancing methodologies will help to identify new pathogenic mechanisms that inform the understanding of biologic subdivisions within JIA. Resulting insights will facilitate the application of lessons learned across the age spectrum to the treatment of arthritis in children and adults.

aDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital

bDivision of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts

cCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA

dInstituto de Investigación Sanitaria Gregorio Marañon, Madrid, Spain

Correspondence to Peter A. Nigrovic, MD, Brigham and Women's Hospital and Boston Children's Hospital, Hale Building for Transformative Medicine 6002-L, 60 Fenwood Road, Boston, MA 02115, USA. Tel: +1 617 525 1031; fax: +1 617 525 1010; e-mail:

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