Title
Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus
Date Issued
01 January 2020
Access level
open access
Resource Type
journal article
Author(s)
Enocsson H.
Wirestam L.
Dahle C.
Padyukov L.
Jönsen A.
Urowitz M.B.
Gladman D.D.
Romero-Diaz J.
Bae S.C.
Fortin P.R.
Sanchez-Guerrero J.
Clarke A.E.
Bernatsky S.
Gordon C.
Hanly J.G.
Wallace D.J.
Isenberg D.A.
Rahman A.
Merrill J.T.
Ginzler E.
Chatham W.W.
Petri M.
Khamashta M.
Aranow C.
Mackay M.
Dooley M.A.
Manzi S.
Ramsey-Goldman R.
Nived O.
Steinsson K.
Zoma A.A.
Ruiz-Irastorza G.
Lim S.S.
Kalunian K.C.
Inanc M.
van Vollenhoven R.F.
Ramos-Casals M.
Kamen D.L.
Jacobsen S.
Peschken C.A.
Askanase A.
Stoll T.
Bruce I.N.
Wetterö J.
Sjöwall C.
University of Alabama at Birmingham
Publisher(s)
Academic Press
Abstract
Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. Methods: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). Results: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). Conclusion: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.
Volume
106
Language
English
OCDE Knowledge area
Reumatología
Inmunología
Patología
Subjects
Scopus EID
2-s2.0-85073722485
PubMed ID
Source
Journal of Autoimmunity
ISSN of the container
08968411
DOI of the container
10.1016/j.jaut.2019.102340
Sponsor(s)
This study was funded by grants from the Swedish Rheumatism Association , the Region Östergötland (ALF Grants) , the King Gustaf V's 80-year Anniversary Foundation , and the King Gustaf V and Queen Victoria's Freemasons Foundation . Dr. Bruce is a National Institute for Health Research (NIHR) Senior Investigator and is funded by Versus Arthritis , the NIHR Manchester Biomedical Research Centre , and the NIHR /Welcome Trust Manchester Clinical Research Facility. Dr. Caroline Gordon is supported by Lupus UK, the Sandwell and West Birmingham Hospitals NHS Trust , and the National Institute for Health Research (NIHR)/ Wellcome Trust Birmingham Clinical Research Facility . The views expressed are those of the author(s) and are not necessarily those of the NHS, the NIHR or the Department of Health. Rosalind Ramsey-Goldman's work was supported by the NIH (grants 8UL1TR000150 , formerly UL-1RR-025741 , K24-AR-02318 and P60AR064464 , formerly P60-AR-48098 ). Dr. Sang-Cheol Bae's work was supported in part by funding ( NRF-2017M3A9B4050335 ) from the National Research Foundation of Korea .
We thank the EIRA study personnel for providing us with information and sera from healthy controls. Nicole Anderson and Anne MacKinnon are acknowledged for biobank handling and data management. This study was funded by grants from the Swedish Rheumatism Association, the Region ?sterg?tland (ALF Grants), the King Gustaf V's 80-year Anniversary Foundation, and the King Gustaf V and Queen Victoria's Freemasons Foundation. Dr. Bruce is a National Institute for Health Research (NIHR) Senior Investigator and is funded by Versus Arthritis, the NIHR Manchester Biomedical Research Centre, and the NIHR/Welcome Trust Manchester Clinical Research Facility. Dr. Caroline Gordon is supported by Lupus UK, the Sandwell and West Birmingham Hospitals NHS Trust, and the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. The views expressed are those of the author(s) and are not necessarily those of the NHS, the NIHR or the Department of Health. Rosalind Ramsey-Goldman's work was supported by the NIH (grants 8UL1TR000150, formerly UL-1RR-025741, K24-AR-02318 and P60AR064464, formerly P60-AR-48098). Dr. Sang-Cheol Bae's work was supported in part by funding (NRF-2017M3A9B4050335) from the National Research Foundation of Korea.
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