HLA-DRB1*11and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis
Authors: Ombrello Michael J. , Remmers Elaine F. , Tachmazidou Ioanna , Grom Alexei , Foell Dirk , Haas Johannes-Peter , Martini Alberto , Gattorno Marco , Özen Seza , Prahalad Sampath , Zeft Andrew S. , Bohnsack John F. , Mellins Elizabeth D. , Ilowite Norman T. , Russo Ricardo , Len Claudio , Hilario Maria Odete E. , Oliveira Sheila , Yeung Rae S. M. , Rosenberg Alan , Wedderburn Lucy R. , Anton Jordi , Schwarz Tobias , Hinks Anne , Bilginer Yelda , Park Jane , Cobb Joanna , Satorius Colleen L. , Han Buhm , Baskin Elizabeth , Signa Sara , Duerr Richard H. , Achkar J. P. , Kamboh M. Ilyas , Kaufman Kenneth M. , Kottyan Leah C. , Pinto Dalila , Scherer Stephen W. , Alarcón-Riquelme Marta E. , Docampo Elisa , Estivill Xavier , Gül Ahmet ,   British Society of Pediatric and Adolescent Rheumatology (BSPAR) 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, de Bakker Paul I. W. , Raychaudhuri Soumya , Langefeld Carl D. , Thompson Susan , Zeggini Eleftheria , Thomson Wendy , Kastner Daniel L. , Woo Patricia ,   the International Childhood Arthritis Genetics (INCHARGE) Consortium, Achkar J. P. , Alarcón-Riquelme Marta E. , Allen Roger , Anton Jordi , Baskin Elizabeth , Berg Stefan , Bica Bianca , Bilginer Yelda , Bohnsack John F. , Cavalcanti Andre , Chaitow Jeffrey , Cobb Joanna , Cuttica Rubin , de Bakker Paul I. W. , Docampo Elisa , Duerr Richard , Ellis Justine , Estivill Xavier , Finkel Terri H. , Foell Dirk , Gattorno Marco , Grom Alexei , Gül Ahmet , Haas Johannes-Peter , Hakonarson Hakon , Han Buhm , Hilario Maria Odete E. , Hinks Anne , Ilowite Norman T. , Kamboh M. Ilyas , Kastner Daniel L. , Kaufman Kenneth , Kottyan Leah C. , Langefeld Carl , Len Claudio , Martini Alberto , Mellins Elizabeth D. , Minden Kirstin , Murray Kevin , Oliveira Sheila , Ombrello Michael J. , Ozen Seza , Park Jane , Pinto Dalila , Prahalad Sampath , Quartier Pierre , Raychaudhuri Soumya , Remmers Elaine F. , Rosenberg Alan , Russo Ricardo , Satorius Colleen , Scherer Stephen W. , Schneider Rayfel , Schwarz Tobias , Singh-Gerwal Davinder , Tachmazidou Ioanna , Thompson Susan , Thomson Wendy , Wedderburn Lucy R. , Woo Patricia , Wulffraat Nico , Yeung Rae SM , Zeft Andrew S. , Zeggini Eleftheria , Abinum Mario , Bell A. , Craft Alan W. , Crawley Esther , David Joel , Foster Helen , Gardener-Medwin Janet , Griffin Jane , Hall Ann , Hall M. , Herrick Ariane L. , Hollingworth Peter , Holt Lennox , Jones Stan , Pountain Gillian , Ryder Clive , Southwood Tauny , Stewart I. , Venning Helen , Wedderburn Lucy R. , Woo Patricia , Wyatt Sue , Baildam Eileen , Bishop Nick , Brown Lynsey , Buckley Joanne , Chieng Alice , Carrasco Roberto , Cobb Joanna , Cook Lucy , Davidson Joyce , Duggan Annette , Eltringham Michael , Foster Helen , Friel Elizabeth , Friswell Mark , Gardner-Medwin Janet , Gilbert Paul , Gould Vikki , Hadfield Kelly , Hyrich Kimme , Jones Julie , Lal Sham , Lay Mark , Lloyd Gabrielle , Lloyd Olivia , Lydon Carol , Makengo Natasha , McGovern Ann , Meijer Alexandra , Mills-Wierda Nicola , Moorcroft Theresa , Price Vicki , Qiao Liang , Riding Kay , Sim Jane , Southwood Tauny , Thomson Wendy , Todd Maureen , Tremble Susan , Venter Katharine , Wade Debbie , Ward Peter , Watson Sharon , Webster Gwen , Wedderburn Lucy R , Zelenovic Jadranka , Birmingham James D. , Elder Melissa , Gottlieb Beth S. , Ilowite Normal T. , Imundo Lisa F. , Kimura Yukiko , Lokhnygina Yuliya , Miller Michael L. , Milojevic Diana , O'Neil Kathleen , Punaro Marilynn G. , Prather Kristi , Ruth Natasha M. , Sandborg Christy I. , Schanberg Laura E. , Sherry David D. , Singer Nora G. , Spalding Steven J. , Tarvin Stacey E. , Verbsky James W. , Wallace Carol A. , Zemel Lawrence S. , Burkle Katrin , Cobb Joanna , Etheridge Angela , Gilbert Paul , Hinks Anne , Hirani Shashi , Kassoumeri Laura , Lal Sham , Melville Laura , Moncrieffe Halima , Mulligan Kathleen , Newman Stanton , Patrick Fiona , Southwood Tauny , Thomson Wendy , Ursu Simona , Wedderburn Lucy R , Whitworth Pamela , Woo Patricia , Baxter-Jones Adam , Benseler Susanne , Boire Gilles , Cabral David A. , Cameron Bonnie , Campillo Sarah , Chedeville Gaëlle , Chetaille Anne-Laure , Dancey Paul , Duffy Ciaran , Duffy Karen Watanabe , Ellsworth Janet , Feldman Brian , Gibbon Michele , Guillet Chantal , Guzman Jaime , Houghton Kristin , Huber Adam , Jurencak Roman , Lang Bianca , Laxer Ronald , Maenz Lynn , Matheson Loren , Oen Kiem , Petty Ross , Ramsey Suzanne , Rezaei Elham , Rosenberg Alan , Roth Johannes , Schneider Rayfel , Scuccimarri Rosie , Silverman Earl , Spiegel Lynn , Stringer Elizabeth , Tse Shirley , Tucker Lori B. , Turvey Stuart , Yeung Rae SM 
Published: November 2015

Significance

To determine whether genetic variation within the MHC locus influences the risk of developing systemic juvenile idiopathic arthritis (sJIA), we examined a dense set of MHC region single nucleotide polymorphisms, classic HLA alleles, and the individual amino acids of HLA molecules in nine independent sJIA case-control populations. Association testing revealed that genetic variants within the MHC class II gene cluster significantly influenced sJIA risk in every study population. The strongest risk factor for sJIA wasHLA-DRB1*11, which conferred at least a two-fold increase in disease risk in each population studied. These data implicate the interaction of antigen presenting cells with T cells in the pathogenesis of sJIA.