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Title: Genetic architecture distinguishes systemic juvenile idiopathic arthritis from otherforms 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
Ozen, Seza
Prahalad, Sampath
Zeft, Andrew S.
Bohnsack, John F.
Ilowite, Norman T.
Mellins, Elizabeth D.
Russo, Ricardo
Len, Claudio
Odete e Hilario, Maria
Oliveira, Sheila
Yeung, Rae S. M.
Rosenberg, Alan M.
Wedderburn, Lucy R.
Antón López, 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 C.
Pinto, Dalila
Scherer, Stephen W.
Alarcón-Riquelme, Marta E.
Docampo Martínez, Elisa
Estivill, Xavier, 1955-
Gül, Ahmet
British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group
Inception Cohort of Newly Diagnosed Patients with Juvenile Idiopathic Arthritis (ICON-JIA) Study Group
Childhood Arthritis Prospective Study (CAPS) Group
Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators
Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group
Biologically Based Outcome Predictors in JIA (BBOP) Group Carl D Langefeld
Thompson, Susan
Zeggini, Eleftheria
Kastner, Daniel L.
Woo, Patricia
Thomson, Wendy
Keywords: Artritis
Genètica humana
Human genetics
Issue Date: 7-Dec-2016
Publisher: BMJ Publishing Group
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.
Note: Reproducció del document publicat a:
It is part of: Annals of the Rheumatic Diseases, 2016, vol. 2016
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ISSN: 0003-4967
Appears in Collections:Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)

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