Osteopontin and Disease Activity in Patients with Recent-onset Systemic Lupus Erythematosus: Results from the SLICC Inception Cohort

• Type of Material: Article
• Authors: Lina Wirestam, Linkoping University; Helena Enocsson, Linkoping University; Thomas Skogh, Linkoping University; Leonid Padyukov, Karolinska Institutet; Andreas Jonsen, Lund University; Murray B. Urowitz, Toronto Western Hospital; Dafna Gladman, Toronto Western Hospital; Juanita Romero-Diaz, Instituto Nacional de Ciencias Medicas y Nutrición; Sang-Cheol Bae, Hanyang University; Paul R. Fortin, Laval University; Jorge Sanchez-Guerrero, University of Toronto; Ann Clarke, University of Calgary; Sasha Bernatsky, McGill University; Caroline Gordon, University of Birmingham; John G. Hanly, Queen Elizabeth II Health Sciences Centre and Dalhousie University; Daniel Wallace, University of California Los Angeles; David Isenberg, University College London; Anisur Rahman, University College London; Joan Merrill, Oklahoma Medical Research Foundation; Ellen Ginzler, SUNY New York; Graciela S. Alarcon, University of Alabama Birmingham; W. Winn Chatham, University of Alabama Birmingham; Michelle Petri, Johns Hopkins University; Munther Khamashta, St Thomas Hospital; Cynthia Aranow, Feinstein Institute for Medical Research; Meggan Mackay, Feinstein Institute for Medical Research; Mary Anne Dooley, University of North Carolina; Susan Manzi, Autoimmun Institute; Rosalind Ramsey-Goldman, Northwestern University; Ola Nived, Lund University; Kristjan Steinsson, Fossvogur Landspitali University Hospital; Asad Zoma, Hairmyres Hospital; Guillermo Ruiz-Irastorza, University of Basque Country; Sung Lim, Emory University; Ken Kalunian, University of California San Diego; Murat Inanc, Istanbul University; Ronald van Vollenhoven, Karolinska University; Manuel Ramos-Casals, IDIBAPS; Diane L. Kamen, Medical University of South Carolina; Soren Jacobsen, Copenhagen University Hospital; Christine Peschken, University of Manitoba; Anca Askanase, Columbia University; Thomas Stoll, Kantousspital; Ian N. Bruce, University of Manchester; Jonas Wettero, Linkoping University; Christopher Sjowall, Linkoping University
• Language: English
• Date: 2019-05-01
• Publisher: Journal of Rheumatology Publishing Company
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: The Journal of Rheumatology Copyright © 2019. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.3899/jrheum.180713
• Title of Journal or Parent Work: Journal of Rheumatology
• Volume: 46
• Issue: 5
• Start Page: 492
• End Page: 500
• Grant/Funding Information: None declared
• Keywords: Life Sciences & Biomedicine; Rheumatology; Osteopontin; Disease activity; Index; Expression; Prognosis; Macrophage infiltration; Science & Technology; Associations; Population; Biomarkers; Organ damage; Systemic lupus erythematosus
• Research Categories: Biology, Neuroscience; Biology, Physiology; Health Sciences, Immunology; Health Sciences, Rehabilitation and Therapy

Abstract

Objective In cross-sectional studies, elevated osteopontin (OPN) has been proposed to reflect, and/or precede, progressive organ damage and severity in systemic lupus erythematosus (SLE). We aimed, in a prospective cohort of recent-onset SLE to determine whether raised serum OPN associates with disease activity and/or precedes organ damage. Methods We included 345 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5-years of follow-up data available. All patients fulfilled the 1982 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual follow-up visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results Compared to controls, baseline OPN was raised fourfold in SLE cases (p<0.0001). A weak correlation was found between baseline OPN and accrual of global damage (r=0.16, p=0.004) at 5 years. OPN levels predicted damage when defined as SDI≥1 (p=0.024), but the damage-predictive value was lost when adjusting damage cut-off to SDI≥2. Baseline OPN correlated with disease activity at inclusion (r=0.27, p<0.0001). Patients with high disease activity (SLEDAI-2K≥5) had raised serum OPN (p<0.0001). Higher OPN levels were also found in patients with persistently raised disease activity (p=0.0005). Conclusions Raised OPN at SLE onset was associated with higher disease activity and more severe disease and may as a biomarker help to guide more targeted attempts to control disease activity over time.