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

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

Detection of multifocal osteonecrosis in an adolescent with dermatomyositis using whole-body MRI

Osteonecrosis is a well-recognized complication of corticosteroid use resulting in significant morbidity, often requiring surgical intervention. Whole-body MRI is a promising method that allows imaging of the whole patient in a reasonable time without the use of ionizing radiation. This technique has the potential for evaluating nonmalignant multifocal skeletal disease like osteonecrosis. This case highlights the value of whole-body MR in an adolescent with dermatomyositis who developed multifocal osteonecrosis.Universidade Federal de São Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, BR-04025002 São Paulo, BrazilUniversidade Federal de São Paulo, Image Diag Dept, BR-04025002 São Paulo, BrazilSt Jude Childrens Hosp, Dept Radiol Sci, Div Diagnost Imaging, Memphis, TN 38105 USAUniversidade Federal de São Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, BR-04025002 São Paulo, BrazilUniversidade Federal de São Paulo, Image Diag Dept, BR-04025002 São Paulo, BrazilWeb of Scienc

Genetic Architecture of Systemic Juvenile Idiopathic Arthritis Distinguishes It from Oligoarticular and Polyarticular Forms of Juvenile Idiopathic Arthritis

NIAMS, Translat Genet & Genom Unit, NIH, Bethesda, MD USANHGRI, NIH, Bethesda, MD 20892 USAUniv Manchester, ARC Epidemiol Unit, Manchester, Lancs, EnglandCincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USAUniv Munster, Munster, GermanyIst Giannina Gaslini, Genoa, ItalyIst Giannina Gaslini, UO Pediat 2, Genoa, ItalyHacettepe Univ, Fac Med, Dept Pediat, Ankara, TurkeyEmory Univ, Sch Med, Pediat Rheumatol, Atlanta, GA USACleveland Clin, Pediat Rheumatol, Cleveland, OH 44106 USAUniv Utah, Div Allergy Immunol & Pediat Rheumatol, Salt Lake City, UT USAChildrens Hosp Montefiore, Rheumatol, Bronx, NY USAHosp Pediat Garrahan, Buenos Aires, DF, ArgentinaStanford Univ, Med Ctr, Dept Pediat CCSR, Stanford, CA 94305 USAUniv Fed Sao Paulo, Pediat, Sao Paulo, BrazilPRCSG, Cincinnati, OH USAUniv Fed Rio de Janeiro, Pediat Rheumatol, Rio De Janeiro, BrazilHosp Sick Children, Div Rheumatol, Toronto, ON, CanadaUCL, Inst Child Hlth, London, EnglandHosp St Joan de Deu, Unitat Reumatol Pediat, Barcelona, SpainGerman Ctr Pediat & Adolescent Rheumatol, Garmisch Partenkirchen, GermanyChildrens Hosp Dresden, Dresden, GermanyUniv Aachen, Aachen, GermanyCincinnati Childrens Hosp, Div Rheumatol, Cincinnati, OH USANHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USAUCL, Sch Med, Great Ormond St Hosp, London, EnglandUniv Manchester, Arthrit Res UK Ctr Genet & Genom, Manchester, Lancs, EnglandPediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo,, BrazilWeb of Scienc

Animated drawings rendered by genetic programming

We describe an approach to generating animations of drawings that start as a random collection of strokes and gradually resolve into a recognizable subject. The strokes are represented as tree based genetic programs. An animation is generated by rendering the best individual in a generation as a frame of a movie. The resulting animations have an engaging characteristic in which the target slowly emerges from a random set of strokes. We have generated two qualitatively different kinds of animations, ones that use grey level straight line strokes and ones that use binary Bezier curve stokes. Around 100,000 generations are needed to generate engaging animations. Population sizes of 2 and 4 give the best convergence behaviour. Convergence can be accelerated by using information from the target in drawing a stroke. Our approach provides a large range of creative opportunities for artists. Artists have control over choice of target and the various stroke parameters

HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA