Research ArticleArticle
S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis
Faekah Gohar, Janneke Anink, Halima Moncrieffe, Lisette W.A. Van Suijlekom-Smit, Femke H.M. Prince, Marion A.J. van Rossum, Koert M. Dolman, Esther P.A.H. Hoppenreijs, Rebecca ten Cate, Simona Ursu, Lucy R. Wedderburn, Gerd Horneff, Michael Frosch, Dirk Foell and Dirk Holzinger
The Journal of Rheumatology January 2018, jrheum.170438; DOI: https://doi.org/10.3899/jrheum.170438
Faekah Gohar
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Janneke Anink
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Halima Moncrieffe
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Lisette W.A. Van Suijlekom-Smit
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Femke H.M. Prince
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Marion A.J. van Rossum
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Koert M. Dolman
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Esther P.A.H. Hoppenreijs
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Rebecca ten Cate
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Simona Ursu
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Lucy R. Wedderburn
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Gerd Horneff
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Michael Frosch
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Dirk Foell
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Dirk Holzinger
From the Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster, Münster, Germany; Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam, Rotterdam, the Netherlands; Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, Ohio, USA; Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis, Amsterdam; Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre, Nijmegen; Leiden University Medical Centre, Leiden, the Netherlands; School of Biological Sciences, Royal Holloway, University of London; Infection, Immunity, Inflammation Programme, University College London (UCL) Great Ormond Street (GOS) Institute of Child Health; UK National Institute for Health Research (NIHR) GOS Hospital Biomedical Research Centre (BRC); Arthritis Research UK Centre for Adolescent Rheumatology at UCL, London, UK; Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin; German Pediatric Pain Centre, Children’s and Adolescents’ Hospital, Datteln; Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Essen, Germany. F.G. was supported by the European Union Seventh Framework Programme (FP7) EUTRAIN (ref.289903) grant. L.W. is supported by the Great Ormond Street Hospital Children’s Charity. D.H. and D.F. were funded by the Interdisciplinary Centre of Clinical Research at the University of Münster (IZKF CRA04) and received an unconditional grant from Pfizer Germany for this study. H.M. was supported in part by the US National Institutes of Health (NIH) Grant Award Nos. P30 AR070549, R01 HD089928, U01 AI130830. The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH. The ABC register is maintained with unconditional support from the Dutch Board of Health Insurances (2003-2006), Pfizer, and AbbVie. The BIKeR Registry is supported by an unconditional grant from Pfizer Germany and also the FP7 grant, EC-GA 305266 MIAMI. The CHARMS study was funded by SPARKS UK (08ICH09), the Big Lottery Fund UK (RG/1/010135231), UK Medicines for Children Research Network (NIHRfunded), and NIHR GOS BRC. F. Gohar, MD, Department of Pediatric Rheumatology and Immunology, University Children’s Hospital Münster; J. Anink, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; H. Moncrieffe, PhD, Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati; L.W. Van Suijlekom-Smit, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; F.H. Prince, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Erasmus MC Sophia Children’s Hospital Rotterdam; M.A. van Rossum, MD, PhD, Emma Children’s Hospital, Academic Medical Centre and Amsterdam Rheumatology and Immunology Centre, Reade location, Jan van Breemen Institute; K.M. Dolman, MD, PhD, Department of Pediatrics/Pediatric Rheumatology, Onze Lieve Vrouwe Gasthuis; E.P. Hoppenreijs, MD, Department of Pediatrics/Pediatric Rheumatology, St. Maartenskliniek and Radboud University Medical Centre; R. ten Cate, MD, PhD, Leiden University Medical Centre; S. Ursu, PhD, School of Biological Sciences, Royal Holloway, University of London; L.R. Wedderburn, MD, PhD, Infection, Immunity, Inflammation Programme, UCL GOS Institute of Child Health, UCL; G. Horneff, MD, Centre of Pediatric Rheumatology, Department of General Pediatrics, Asklepios Clinic Sankt Augustin; M. Frosch, MD, German Pediatric Pain Centre, Children’s and Adolescents’ Hospital; D. Foell, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster; D. Holzinger, MD, Department of Paediatric Rheumatology and Immunology, University Children’s Hospital Münster, and Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen. Address correspondence to Dr. D. Holzinger, Klinik für Kinderheilkunde III, Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstraße 55, 45147 Essen, Germany. E-mail: Dirk.Holzinger@uk-essen.de. Accepted for publication September 22, 2017.
Abstract
Objective Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response.
Methods S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded.
Results Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133–440 ng/ml] and MTX (median 220, IQR 100–440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125–615) ng/ml versus 150 (IQR 87–233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150–624) ng/ml versus 151 (IQR 83–201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10.
Conclusion Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.
In this issue
The Journal of Rheumatology
Vol. 49, Issue 5
1 May 2022
S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis
Faekah Gohar, Janneke Anink, Halima Moncrieffe, Lisette W.A. Van Suijlekom-Smit, Femke H.M. Prince, Marion A.J. van Rossum, Koert M. Dolman, Esther P.A.H. Hoppenreijs, Rebecca ten Cate, Simona Ursu, Lucy R. Wedderburn, Gerd Horneff, Michael Frosch, Dirk Foell, Dirk Holzinger
The Journal of Rheumatology Jan 2018, jrheum.170438; DOI: 10.3899/jrheum.170438
S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis
Faekah Gohar, Janneke Anink, Halima Moncrieffe, Lisette W.A. Van Suijlekom-Smit, Femke H.M. Prince, Marion A.J. van Rossum, Koert M. Dolman, Esther P.A.H. Hoppenreijs, Rebecca ten Cate, Simona Ursu, Lucy R. Wedderburn, Gerd Horneff, Michael Frosch, Dirk Foell, Dirk Holzinger
The Journal of Rheumatology Jan 2018, jrheum.170438; DOI: 10.3899/jrheum.170438
