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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.
systemic juvenile idiopathic arthritis, Still’s disease, human leukocyte antigen, autoinflammation
HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis
Michael J. Ombrello,a,1 Elaine F. Remmers,b Ioanna Tachmazidou,c Alexei Grom,d,e Dirk Foell,f Johannes-Peter Haas,g Alberto Martini,h,i Marco Gattorno,i Seza ozen,j Sampath Prahalad,k,l Andrew S. Zeft,m John F. Bohnsack,n Elizabeth D. Mellins,o Norman T. Ilowite,p Ricardo Russo,q Claudio Len,r Maria Odete E. Hilario,r Sheila Oliveira,s Rae S. M. Yeung,t,u,v Alan Rosenberg,w Lucy R. Wedderburn,x,y Jordi Anton,z Tobias Schwarz,aa Anne Hinks,bb Yelda Bilginer,j Jane Park,o Joanna Cobb,bb,cc Colleen L. Satorius,b Buhm Han,dd,ee,ff Elizabeth Baskin,a Sara Signa,h Richard H. Duerr,gg,hh J. P. Achkar,ii,jj M. Ilyas Kamboh,gg Kenneth M. Kaufman,d,e Leah C. Kottyan,d,e Dalila Pinto,kk Stephen W. Scherer,ll Marta E. Alarcon-Riquelme,mm,nn Elisa Docampo,oo,pp Xavier Estivill,pp Ahmet Gul,qq British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group,2 Childhood Arthritis Prospective Study (CAPS) Group,2 Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators,2 Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group,2 Biologically Based Outcome Predictors in JIA (BBOP) Group,2 Paul I. W. de Bakker,rr,ss,tt Soumya Raychaudhuri,bb,dd,ee Carl D. Langefeld,uu Susan Thompson,d,e Eleftheria Zeggini,c Wendy Thomson,bb,cc Daniel L. Kastner,b,1 Patricia Woo,y and the International Childhood Arthritis Genetics (INCHARGE) Consortium2
2015 Dec 29
Regular school sports can help adolescents achieve the recommended amount of daily physical activity and provide knowledge, attitudes and behavioral skills that are needed in order to adopt and maintain a physically active lifestyle. Furthermore, it reaches all children including those that are at risk for engaging in more sedentary types of behavior. Since adolescents with juvenile idiopathic arthritis (JIA) are less involved in physical and social activities than their healthy peers, the objectives were to (1) estimate the prevalence of participation in school sports among patients with JIA; (2) determine the correlates associated with school sports absenteeism; and (3) investigate whether attendance in school sports has changed in the era of biologics.
Data from schoolchildren with JIA recorded in the German National Paediatric Rheumatologic Database (NPRD) in the years 2000 to 2015 were considered for the analyses. Data from the year 2015 were inspected to analyze correlates of school sports absenteeism. Whether school sports participation had changed between 2000 and 2015 was determined using linear mixed models.
During the 15-year period, the participation rates in school sports were determined in 23,016 patients. The proportion of patients who participated in school sports almost always steadily increased from 31% in 2000 to 64% in 2015 (β = 0.017, 95% confidence interval (CI) 0.015, 0.020), whereas the exemption rate simultaneously decreased from 44% in 2000 to 16% in 2015 [β = − 0.009, 95% CI -0.011, − 0.007]. In 2015, the data from 5879 patients (mean age 13.1 ± 3.3 years, female 65%, disease duration 5.9 ± 4.0 years, persistent oligoarthritis 37%) were available for evaluation. Full exemption from school sports (in 16.1% of cases) was associated with functional limitations, disease activity and any use of DMARDs, intra-articular glucocorticoid injections or physiotherapy.
School sports attendance among children and adolescents with JIA has increased significantly over the past 15 years. Possible explanations include improved functional ability probably due to better treatment options. The integration of patients with child acceptable symptom states who have previously been fully exempted from school sports needs to be addressed in the future.
Juvenile idiopathic arthritis, School sports, Prevalence, Correlates, Trends, Children and adolescents, Participation
Participation in school sports among children and adolescents with juvenile idiopathic arthritis in the German National Paediatric Rheumatologic Database, 2000-2015: results from a prospective observational cohort study
Florian Milatz,corresponding author1 Jens Klotsche,1 Martina Niewerth,1 Nils Geisemeyer,1 Ralf Trauzeddel,2 Elisabeth Weißbarth-Riedel,3 Tilmann Kallinich,4 Joachim Peitz,5 Matthias Hartmann,6 and Kirsten Minden7
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analyzed. Binomial Generalized Linear Mixed Models were fit.
17,158 participants (2,287 major depression cases) from 57 primary studies were analyzed. Among fully structured interviews, odds of major depression were higher for the MINI compared to the Composite International Diagnostic Interview (CIDI) [OR (95% CI) = 2.10 (1.15-3.87)]. Compared to semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression [OR (95% CI) = 3.13 (0.98-10.00)], similarly likely for moderate-level symptoms (PHQ-9 scores 7-15) [OR (95% CI) = 0.96 (0.56-1.66)], and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) [OR (95% CI) = 0.50 (0.26-0.97)].
The MINI may identify more depressed cases than the CIDI, and semi- and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Probability of major depression diagnostic classification using semi-structured vs. fully structured diagnostic interviews
Brooke Levis, MSc, Andrea Benedetti, PhD, Kira E. Riehm, MSc, Nazanin Saadat, BSc, Alexander W. Levis, BSc, Marleine Azar, BSc, Danielle B. Rice, MSc, Matthew J. Chiovitti, MISt, Tatiana A. Sanchez, BSc, Pim Cuijpers, PhD, Simon Gilbody, PhD, John P. A. Ioannidis, MD, Lorie A. Kloda, PhD, Dean McMillan, PhD, Scott B. Patten, MD, Ian Shrier, MD, Russell J. Steele, PhD, Roy C. Ziegelstein, MD, Dickens H. Akena, PhD, Bruce Arroll, MBChB, Liat Ayalon, PhD, Hamid R. Baradaran, MD, Murray Baron, MD, Anna Beraldi, PhD, Charles H. Bombardier, PhD, Peter Butterworth, PhD, Gregory Carter, FRANZCP, Marcos H. Chagas, MD, Juliana C. N. Chan, MD, Rushina Cholera, MD, Neerja Chowdhary, MD, Kerrie Clover, PhD, Yeates Conwell, MD, Janneke M. de Man-van Ginkel, PhD, Jaime Delgadillo, PhD, Jesse R. Fann, MD, Felix H. Fischer, PhD, Benjamin Fischler, MD, Daniel Fung, MD, Bizu Gelaye, PhD, Felicity Goodyear-Smith, MD, Catherine G. Greeno, PhD, Brian J. Hall, PhD, John Hambridge, Dip Clin Psych, Patricia A. Harrison, PhD, Ulrich Hegerl, MD, Leanne Hides, PhD(Clin), Stevan E. Hobfoll, PhD, Marie Hudson, MD, Thomas Hyphantis, MD, Masatoshi Inagaki, MD, Khalida Isamail, MD, Nathalie Jette, MD, Mohammad E. Khamseh, MD, Kim M. Kiely, PhD, Femke Lamers, PhD, Shen-Ing Liu, MD, Manote Lotrakul, MD, Sonia R. Loureiro, PhD, Bernd Lowe, MD, Laura Marsh, MD, Anthony McGuire, PhD, Sherina Mohd Sidik, PhD, Tiago N. Munhoz, PhD, Kumiko Muramatsu, MD, Flavia L. Osorio, PhD, Vikram Patel, MD, Brian W. Pence, PhD, Philippe Persoons, MD, Angelo Picardi, MD, Alasdair G. Rooney, MD, Ina S. Santos, MD, Juwita Shaaban, MMed (Fam. Med), Abbey Sidebottom, PhD, Adam Simning, MD, Lesley Stafford, PhD, Sharon Sung, PhD, Pei Lin Lynnette Tan, MMed (Psychiatry), Alyna Turner, PhD, Christina M. van der Feltz-Cornelis, PhD, Henk C. van Weert, MD, Paul A. Vohringer, MD, Jennifer White, PhD, Mary A. Whooley, MD, Kirsty Winkley, PhD, Mitsuhiko Yamada, MD, Yuying Zhang, PhD, and Brett D. Thombs, PhD
2019 Jun 1.