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; Alan M. Rosenberg for the BBOP Study Group

doi:10.3899/jrheum.200391

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

J Rheumatol. 2021 May;48(5):760-766. doi: 10.3899/jrheum.200391. Epub 2020 Oct 15.

Authors

Elham Rezaei¹, Marianna M Newkirk², Zhenhong Li³, John R Gordon⁴, Kiem G Oen⁵, Susanne M Benseler⁶, Gilles Boire⁷, David A Cabral⁸, Sarah Campillo⁹, Gaëlle Chédeville⁹, Anne-Laure Chetaille¹⁰, Paul Dancey¹¹, Ciaran Duffy¹², Karen Watanabe Duffy¹³, Kristin Houghton⁸, Adam M Huber¹⁴, Roman Jurencak¹², Bianca Lang¹⁴, Kimberly A Morishita⁸, Ross E Petty⁸, Suzanne E Ramsey¹⁴, Johannes Roth¹⁵, Rayfel Schneider¹⁶, Rosie Scuccimarri⁹, Lynn Spiegel¹⁶, Elizabeth Stringer¹⁴, Shirley M L Tse¹⁶, Lori B Tucker⁸, Stuart E Turvey⁸, Rae S M Yeung¹⁶, Alan M Rosenberg¹⁷; Alan M. Rosenberg for the BBOP Study Group

Affiliations

¹ E. Rezaei, MD, PhD, A.M. Rosenberg, MD, Departments of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan.
² M.M. Newkirk, PhD, Department of Medicine, McGill University Health Center, Montreal, Quebec.
³ Z. Li, MSc, RC-CHUM, University of Montreal, Montreal, Quebec.
⁴ J.R. Gordon, PhD, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan.
⁵ K.G. Oen, MD, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba.
⁶ S.M. Benseler, MD, PhD, Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Alberta.
⁷ G. Boire, MD, Département de Médecine, Université de Sherbrooke, Sherbrooke, Quebec.
⁸ 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.
⁹ S. Campillo, MD, G. Chédeville, MD, R. Scuccimarri, MD, Department of Pediatrics, McGill University Health Center, Montreal, Quebec.
¹⁰ A.L. Chetaille, MD, Département de Médecine le Centre Hospitalier Universitaire de Quebec, Quebec City, Quebec.
¹¹ P. Dancey, MD, Department of Pediatrics, Janeway Children's Health and Rehabilitation Centre, St. John's, Newfoundland.
¹² C. Duffy, MD, R. Jurencak, MD, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario.
¹³ K. Watanabe Duffy, MD, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario.
¹⁴ 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.
¹⁵ J. Roth, MD, Department of Pediatrics, Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario.
¹⁶ 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.
¹⁷ E. Rezaei, MD, PhD, A.M. Rosenberg, MD, Departments of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan; alan.rosenberg@usask.ca.

PMID: 33060303
DOI: 10.3899/jrheum.200391

Abstract

Objectives: 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.

Keywords: inflammation; juvenile idiopathic arthritis; lipoprotein receptors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Arthritis, Juvenile* / diagnosis
Arthritis, Psoriatic*
Canada
Child
Humans
Lipoproteins, LDL
Low Density Lipoprotein Receptor-Related Protein-1

Substances

Lipoproteins, LDL
Low Density Lipoprotein Receptor-Related Protein-1