TY - JOUR
T1 - Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus
AU - Enocsson, Helena
AU - Wirestam, Lina
AU - Dahle, Charlotte
AU - Padyukov, Leonid
AU - Jönsen, Andreas
AU - Urowitz, Murray B.
AU - Gladman, Dafna D.
AU - Romero-Diaz, Juanita
AU - Bae, Sang Cheol
AU - Fortin, Paul R.
AU - Sanchez-Guerrero, Jorge
AU - Clarke, Ann E.
AU - Bernatsky, Sasha
AU - Gordon, Caroline
AU - Hanly, John G.
AU - Wallace, Daniel J.
AU - Isenberg, David A.
AU - Rahman, Anisur
AU - Merrill, Joan T.
AU - Ginzler, Ellen
AU - Alarcón, Graciela S.
AU - Chatham, W. Winn
AU - Petri, Michelle
AU - Khamashta, Munther
AU - Aranow, Cynthia
AU - Mackay, Meggan
AU - Dooley, Mary Anne
AU - Manzi, Susan
AU - Ramsey-Goldman, Rosalind
AU - Nived, Ola
AU - Steinsson, Kristjan
AU - Zoma, Asad A.
AU - Ruiz-Irastorza, Guillermo
AU - Lim, S. Sam
AU - Kalunian, Kenneth C.
AU - Inanc, Murat
AU - van Vollenhoven, Ronald F.
AU - Ramos-Casals, Manuel
AU - Kamen, Diane L.
AU - Jacobsen, Søren
AU - Peschken, Christine A.
AU - Askanase, Anca
AU - Stoll, Thomas
AU - Bruce, Ian N.
AU - Wetterö, Jonas
AU - Sjöwall, Christopher
N1 - Funding Information:
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 .
Funding Information:
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.
Publisher Copyright:
© 2019 The Authors
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - Organ damage
KW - Outcome
KW - Prognosis
KW - SLE
UR - http://www.scopus.com/inward/record.url?scp=85073722485&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073722485&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2019.102340
DO - 10.1016/j.jaut.2019.102340
M3 - Article
C2 - 31629628
AN - SCOPUS:85073722485
VL - 106
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
M1 - 102340
ER -