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Open Access Research article

Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus

Ornella J Rullo1*, Jennifer MP Woo1, Miriam F Parsa1, Alice DC Hoftman1, Paul Maranian2, David A Elashoff3, Timothy B Niewold4, Jennifer M Grossman2, Bevra H Hahn2, Maureen McMahon2, Deborah K McCurdy1 and Betty P Tsao2*

Author affiliations

1 Department of Pediatrics-Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, MDCC 12-430, Los Angeles, CA, 90095, USA

2 Department of Medicine-Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Avenue, Rehabilitation Building 32-59, Los Angeles, CA, 90095, USA

3 Department of Medicine-General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, 911 Broxton Avenue, Los Angeles, CA, 90095, USA

4 Division of Rheumatology and Department of Immunology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA

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Citation and License

Arthritis Research & Therapy 2013, 15:R18  doi:10.1186/ar4150


See related editorial by Briggs, http://arthritis-research.com/content/15/2/110

Published: 23 January 2013

Abstract

Introduction

Osteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity.

Methods

cOPN and cNGAL were measured in prospectively followed pSLE (n = 42) and adult SLE (aSLE; n = 23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).

Results

Compared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P = 0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r = 0.51 and 0.52, P = 0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P = 0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P = 0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).

Conclusion

High circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.