Associations of clinical and inflammatory biomarker clusters with juvenile idiopathic arthritis categories

Author:

Rezaei Elham1,Hogan Daniel2,Trost Brett2,Kusalik Anthony J2,Boire Gilles3,Cabral David A4,Campillo Sarah5,Chédeville Gaëlle5,Chetaille Anne-Laure6,Dancey Paul7,Duffy Ciaran8,Duffy Karen Watanabe8,Eng Simon W M9,Gordon John10,Guzman Jaime4,Houghton Kristin4,Huber Adam M11,Jurencak Roman8,Lang Bianca11,Laxer Ronald M9,Morishita Kimberly4,Oen Kiem G12,Petty Ross E4,Ramsey Suzanne E11,Scherer Stephen W13,Scuccimarri Rosie5,Spiegel Lynn9,Stringer Elizabeth11,Taylor-Gjevre Regina M10ORCID,Tse Shirley M L9,Tucker Lori B4,Turvey Stuart E4,Tupper Susan1,Wintle Richard F13,Yeung Rae S M9,Rosenberg Alan M1,

Affiliation:

1. Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada

2. Department of Computer Sciences, University of Saskatchewan

3. Département de Médecine, Université de Sherbrooke, Sherbrooke

4. Department of Pediatrics, British Columbia Children's Hospital, Vancouver

5. Department of Pediatrics, McGill University Health Center, Montreal

6. Département de Médecine le Centre Hospitalier Universitaire de Quebec, Quebec

7. Department of Pediatrics, Janeway Children's Health and Rehabilitation Centre, St. John's

8. Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa

9. Department of Pediatrics, University of Toronto and the Hospital for Sick Children, Toronto

10. Department of Medicine, University of Saskatchewan

11. Department of Pediatrics, IWK Health Centre and Dalhousie University, Halifax

12. Department of Pediatrics, University of Manitoba, Winnipeg

13. The Centre for Applied Genomics, Toronto, Canada

Abstract

Abstract Objective To identify discrete clusters comprising clinical features and inflammatory biomarkers in children with JIA and to determine cluster alignment with JIA categories. Methods A Canadian prospective inception cohort comprising 150 children with JIA was evaluated at baseline (visit 1) and after six months (visit 2). Data included clinical manifestations and inflammation-related biomarkers. Probabilistic principal component analysis identified sets of composite variables, or principal components, from 191 original variables. To discern new clinical-biomarker clusters (clusters), Gaussian mixture models were fit to the data. Newly-defined clusters and JIA categories were compared. Agreement between the two was assessed using Kruskal–Wallis analyses and contingency plots. Results Three principal components recovered 35% (three clusters) and 40% (five clusters) of the variance in patient profiles in visits 1 and 2, respectively. None of the clusters aligned precisely with any of the seven JIA categories but rather spanned multiple categories. Results demonstrated that the newly defined clinical-biomarker lustres are more homogeneous than JIA categories. Conclusion Applying unsupervised data mining to clinical and inflammatory biomarker data discerns discrete clusters that intersect multiple JIA categories. Results suggest that certain groups of patients within different JIA categories are more aligned pathobiologically than their separate clinical categorizations suggest. Applying data mining analyses to complex datasets can generate insights into JIA pathogenesis and could contribute to biologically based refinements in JIA classification.

Funder

Canadian Institutes for Health Research

Institutes of Musculoskeletal Health and Arthritis and Infection and Immunity

Arthritis Society

Canadian Arthritis Network

University of Saskatchewan

Manitoba Institute of Child Health

McGill University

Memorial University

University of British Columbia

Division of Pediatric Rheumatology

Clinical Research Centre of the Centre Hospitalier Universitaire de Sherbrooke

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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