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Research ArticleArticle

Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis

Elham Rezaei, Marianna M. Newkirk, Zhenhong Li, John R. Gordon, Kiem G. Oen, Susanne M. Benseler, Gilles Boire, David A. Cabral, Sarah Campillo, Gaëlle Chédeville, Anne-Laure Chetaille, Paul Dancey, Ciaran Duffy, Karen Watanabe Duffy, Kristin Houghton, Adam M. Huber, Roman Jurencak, Bianca Lang, Kimberly A. Morishita, Ross E. Petty, Suzanne E. Ramsey, Johannes Roth, Rayfel Schneider, Rosie Scuccimarri, Lynn Spiegel, Elizabeth Stringer, Shirley M.L. Tse, Lori B. Tucker, Stuart E. Turvey, Rae S.M. Yeung and Alan M. Rosenberg for the BBOP Study Group
The Journal of Rheumatology October 2020, jrheum.200391; DOI: https://doi.org/10.3899/jrheum.200391
Elham Rezaei
The BBOP Study was supported by The Canadian Institutes of Health Research (FRN #82517); The Arthritis Society (Canada), Canadian Arthritis Network (SRI-IJD-01); University of Saskatchewan; The Clinical Research Centre of the Centre Hospitalier Universitaire de Sherbrooke; University of British Columbia; McGill University; Memorial University; Manitoba Institute of Child Health; Children’s Health Research Trust Fund; Jim Pattison Children’s Hospital Foundation of Saskatchewan; The Pediatric Rheumatic Disease Research and Innovation Laboratory, University of Saskatchewan; The Haslam Research Fund, University of Saskatchewan; and The Kleiman Fund, University of Saskatchewan. E. Rezaei, MD, PhD, A.M. Rosenberg, MD, Departments of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan; M.M. Newkirk, PhD, Department of Medicine, McGill University Health Center, Montreal, Quebec; Z. Li, MSc, RC-CHUM, University of Montreal, Montreal, Quebec; J.R. Gordon, PhD, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan; K.G. Oen, MD, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba; S.M. Benseler, MD, PhD, Department of Pediatrics, Alberta Children’s Hospital, University of Calgary, Calgary, Alberta; G. Boire, MD, Département de Médecine, Université de Sherbrooke, Sherbrooke, Quebec; D.A. Cabral, MD, K. Houghton, MD, K.A. Morishita, MD, R.E. Petty, MD, PhD, L.B. Tucker, MD, S.E. Turvey, MD, Department of Pediatrics, British Columbia Children’s Hospital, Vancouver, British Columbia; S. Campillo, MD, G. Chédeville, MD, R. Scuccimarri, MD, Department of Pediatrics, McGill University Health Center, Montreal, Quebec; A.L. Chetaille, MD, Département de Médecine le Centre Hospitalier Universitaire de Quebec, Quebec City, Quebec; P. Dancey, MD, Department of Pediatrics, Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland; C. Duffy, MD, R. Jurencak, MD, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; K. Watanabe Duffy, MD, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; A.M. Huber, MD, B. Lang, MD, S.E. Ramsey, MD, E. Stringer, MD, Department of Pediatrics, IWK Health Centre and Dalhousie University, Halifax, Nova Scotia; J. Roth, MD, Department of Pediatrics, Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario; R. Schneider, MD, L. Spiegel, MD, S.M. Tse, MD, R.S. Yeung, MD, PhD, Department of Paediatrics, University of Toronto and the Hospital for Sick Children, Toronto, Ontario, Canada. The authors declare no conflict of interest. Address correspondence to Dr. A.M. Rosenberg, Department of Pediatrics, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK S7N 0W8, Canada. Email: alan.rosenberg@usask.ca. Accepted for publication October 2, 2020.
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Marianna M. Newkirk
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Zhenhong Li
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John R. Gordon
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Kiem G. Oen
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Susanne M. Benseler
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Gilles Boire
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David A. Cabral
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Sarah Campillo
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Gaëlle Chédeville
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Anne-Laure Chetaille
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Paul Dancey
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Ciaran Duffy
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Karen Watanabe Duffy
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Kristin Houghton
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Adam M. Huber
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Roman Jurencak
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Bianca Lang
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Kimberly A. Morishita
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Ross E. Petty
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Suzanne E. Ramsey
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Johannes Roth
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Rayfel Schneider
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Rosie Scuccimarri
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Lynn Spiegel
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Elizabeth Stringer
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Shirley M.L. Tse
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Lori B. Tucker
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Stuart E. Turvey
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Rae S.M. Yeung
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Alan M. Rosenberg
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Abstract

Objective This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis ( JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity.

Methods Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits.

Results At enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = –0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor–negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later.

Conclusion Plasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.

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The Journal of Rheumatology
Vol. 48, Issue 4
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Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis
Elham Rezaei, Marianna M. Newkirk, Zhenhong Li, John R. Gordon, Kiem G. Oen, Susanne M. Benseler, Gilles Boire, David A. Cabral, Sarah Campillo, Gaëlle Chédeville, Anne-Laure Chetaille, Paul Dancey, Ciaran Duffy, Karen Watanabe Duffy, Kristin Houghton, Adam M. Huber, Roman Jurencak, Bianca Lang, Kimberly A. Morishita, Ross E. Petty, Suzanne E. Ramsey, Johannes Roth, Rayfel Schneider, Rosie Scuccimarri, Lynn Spiegel, Elizabeth Stringer, Shirley M.L. Tse, Lori B. Tucker, Stuart E. Turvey, Rae S.M. Yeung, Alan M. Rosenberg
The Journal of Rheumatology Oct 2020, jrheum.200391; DOI: 10.3899/jrheum.200391

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Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis
Elham Rezaei, Marianna M. Newkirk, Zhenhong Li, John R. Gordon, Kiem G. Oen, Susanne M. Benseler, Gilles Boire, David A. Cabral, Sarah Campillo, Gaëlle Chédeville, Anne-Laure Chetaille, Paul Dancey, Ciaran Duffy, Karen Watanabe Duffy, Kristin Houghton, Adam M. Huber, Roman Jurencak, Bianca Lang, Kimberly A. Morishita, Ross E. Petty, Suzanne E. Ramsey, Johannes Roth, Rayfel Schneider, Rosie Scuccimarri, Lynn Spiegel, Elizabeth Stringer, Shirley M.L. Tse, Lori B. Tucker, Stuart E. Turvey, Rae S.M. Yeung, Alan M. Rosenberg
The Journal of Rheumatology Oct 2020, jrheum.200391; DOI: 10.3899/jrheum.200391
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