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

Author:

Ombrello Michael J,Arthur Victoria L,Remmers Elaine F,Hinks Anne,Tachmazidou Ioanna,Grom Alexei A,Foell Dirk,Martini Alberto,Gattorno Marco,Özen Seza,Prahalad Sampath,Zeft Andrew S,Bohnsack John F,Ilowite Norman T,Mellins Elizabeth D,Russo Ricardo,Len Claudio,Hilario Maria Odete E,Oliveira Sheila,Yeung Rae S M,Rosenberg Alan M,Wedderburn Lucy R,Anton Jordi,Haas Johannes-Peter,Rosen-Wolff Angela,Minden Kirsten,Tenbrock Klaus,Demirkaya Erkan,Cobb Joanna,Baskin Elizabeth,Signa Sara,Shuldiner Emily,Duerr Richard H,Achkar Jean-Paul,Kamboh M Ilyas,Kaufman Kenneth M,Kottyan Leah CORCID,Pinto Dalila,Scherer Stephen W,Alarcón-Riquelme Marta E,Docampo Elisa,Estivill Xavier,Gül Ahmet,Langefeld Carl D,Thompson Susan,Zeggini Eleftheria,Kastner Daniel L,Woo Patricia,Thomson Wendy,

Abstract

ObjectivesJuvenile 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

Publisher

BMJ

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,Immunology and Allergy,Rheumatology

Reference29 articles.

1. Juvenile idiopathic arthritis;Prakken;Lancet,2011

2. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001;Petty;J Rheumatol,2004

3. Rheumatoid arthritis: It's clinical history, etiology, and pathology;Bannatyne;Lancet,1896

4. On a form of chronic joint disease in children;Still;Med Chir Trans,1897

5. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions;Mellins;Nat Rev Rheumatol,2011

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