Paediatrics Publications

Title

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: Clinical and therapeutic implications

Authors

Michael J. Ombrello, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Victoria L. Arthur, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Elaine F. Remmers, National Human Genome Research Institute (NHGRI)
Anne Hinks, Health Innovation Manchester
Ioanna Tachmazidou, Wellcome Sanger Institute
Alexei A. Grom, University of Cincinnati College of Medicine
Dirk Foell, Universitätsklinikum Münster
Alberto Martini, Università degli Studi di Genova
Marco Gattorno, Istituto Giannina Gaslini
Seza Özen, Hacettepe Üniversitesi
Sampath Prahalad, Emory University School of Medicine
Andrew S. Zeft, Cleveland Clinic Foundation
John F. Bohnsack, The University of Utah
Norman T. Ilowite, The Childen's Hospital at Montefiore
Elizabeth D. Mellins, Stanford University
Ricardo Russo, Fundacion Hospital de Pediatria Professor Dr. Juan P. Garrahan
Claudio Len, Universidade Federal de São Paulo
Maria Odete E. Hilario, Universidade Federal de São Paulo
Sheila Oliveira, Universidade Federal do Rio de Janeiro
Rae S.M. Yeung, University of Toronto
Alan M. Rosenberg, University of Saskatchewan, College of Medicine
Lucy R. Wedderburn, UCL Great Ormond Street Institute of Child Health
Jordi Anton, Universitat de Barcelona
Johannes Peter Haas, German Center for Pediatric and Adolescent Rheumatology
Angela Rosen-Wolff, Universitätsklinikum Carl Gustav Carus Dresden
Kirsten Minden, Charité – Universitätsmedizin Berlin
Klaus Tenbrock, Rheinisch-Westfälische Technische Hochschule Aachen
Erkan Demirkaya, Hacettepe ÜniversitesiFollow
Joanna Cobb, Health Innovation Manchester

Document Type

Article

Publication Date

5-1-2017

Journal

Annals of the Rheumatic Diseases

Volume

76

Issue

5

URL with Digital Object Identifier

10.1136/annrheumdis-2016-210324

Abstract

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways.

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