Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus

Helena Enocsson; Lina Wirestam; Charlotte Dahle; Leonid Padyukov; Andreas Jönsen; Murray B Urowitz; Dafna D Gladman; Juanita Romero-Diaz; Sang-Cheol Bae; Paul R Fortin; Jorge Sanchez-Guerrero; Ann E Clarke; Sasha Bernatsky; Caroline Gordon; John G Hanly; Daniel J Wallace; David A Isenberg; Anisur Rahman; Joan T Merrill; Ellen Ginzler; Graciela S Alarcón; W Winn Chatham; Michelle Petri; Munther Khamashta; Cynthia Aranow; Meggan Mackay; Mary Anne Dooley; Susan Manzi; Rosalind Ramsey-Goldman; Ola Nived; Kristjan Steinsson; Asad A Zoma; Guillermo Ruiz-Irastorza; S Sam Lim; Kenneth C Kalunian; Murat Inanc; Ronald F van Vollenhoven; Manuel Ramos-Casals; Diane L Kamen; Søren Jacobsen; Christine A Peschken; Anca Askanase; Thomas Stoll; Ian N Bruce; Jonas Wetterö; Christopher Sjöwall

doi:10.1016/j.jaut.2019.102340

Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus

Helena Enocsson, Lina Wirestam, Charlotte Dahle, Leonid Padyukov, Andreas Jönsen, Murray B Urowitz, Dafna D Gladman, Juanita Romero-Diaz, Sang-Cheol Bae, Paul R Fortin, Jorge Sanchez-Guerrero, Ann E Clarke, Sasha Bernatsky, Caroline Gordon, John G Hanly, Daniel J Wallace, David A Isenberg, Anisur Rahman, Joan T Merrill, Ellen GinzlerGraciela S Alarcón, W Winn Chatham, Michelle Petri, Munther Khamashta, Cynthia Aranow, Meggan Mackay, Mary Anne Dooley, Susan Manzi, Rosalind Ramsey-Goldman, Ola Nived, Kristjan Steinsson, Asad A Zoma, Guillermo Ruiz-Irastorza, S Sam Lim, Kenneth C Kalunian, Murat Inanc, Ronald F van Vollenhoven, Manuel Ramos-Casals, Diane L Kamen, Søren Jacobsen, Christine A Peschken, Anca Askanase, Thomas Stoll, Ian N Bruce, Jonas Wetterö, Christopher Sjöwall

Department for Rheumatology and Spine Diseases

29 Citations (Scopus)

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.

Original language	English
Article number	102340
Journal	Journal of Autoimmunity
Volume	106
Pages (from-to)	102340
ISSN	0896-8411
DOIs	https://doi.org/10.1016/j.jaut.2019.102340
Publication status	Published - Jan 2020

Keywords

Biomarker
Organ damage
Outcome
Prognosis
SLE

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10.1016/j.jaut.2019.102340

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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., ... Sjöwall, C. (2020). Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus. Journal of Autoimmunity, 106, 102340. Article 102340. https://doi.org/10.1016/j.jaut.2019.102340

Enocsson, H, Wirestam, L, Dahle, C, Padyukov, L, Jönsen, A, Urowitz, MB, Gladman, DD, Romero-Diaz, J, Bae, S-C, Fortin, PR, Sanchez-Guerrero, J, Clarke, AE, Bernatsky, S, Gordon, C, Hanly, JG, Wallace, DJ, Isenberg, DA, Rahman, A, Merrill, JT, Ginzler, E, Alarcón, GS, Chatham, WW, Petri, M, Khamashta, M, Aranow, C, Mackay, M, Dooley, MA, Manzi, S, Ramsey-Goldman, R, Nived, O, Steinsson, K, Zoma, AA, Ruiz-Irastorza, G, Lim, SS, Kalunian, KC, Inanc, M, van Vollenhoven, RF, Ramos-Casals, M, Kamen, DL, Jacobsen, S, Peschken, CA, Askanase, A, Stoll, T, Bruce, IN, Wetterö, J & Sjöwall, C 2020, 'Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus', Journal of Autoimmunity, vol. 106, 102340, pp. 102340. https://doi.org/10.1016/j.jaut.2019.102340

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title = "Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus",

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.",

keywords = "Biomarker, Organ damage, Outcome, Prognosis, SLE",

author = "Helena Enocsson and Lina Wirestam and Charlotte Dahle and Leonid Padyukov and Andreas J{\"o}nsen and Urowitz, {Murray B} and Gladman, {Dafna D} and Juanita Romero-Diaz and Sang-Cheol Bae and Fortin, {Paul R} and Jorge Sanchez-Guerrero and Clarke, {Ann E} and Sasha Bernatsky and Caroline Gordon and Hanly, {John G} and Wallace, {Daniel J} and Isenberg, {David A} and Anisur Rahman and Merrill, {Joan T} and Ellen Ginzler and Alarc{\'o}n, {Graciela S} and Chatham, {W Winn} and Michelle Petri and Munther Khamashta and Cynthia Aranow and Meggan Mackay and Dooley, {Mary Anne} and Susan Manzi and Rosalind Ramsey-Goldman and Ola Nived and Kristjan Steinsson and Zoma, {Asad A} and Guillermo Ruiz-Irastorza and Lim, {S Sam} and Kalunian, {Kenneth C} and Murat Inanc and {van Vollenhoven}, {Ronald F} and Manuel Ramos-Casals and Kamen, {Diane L} and S{\o}ren Jacobsen and Peschken, {Christine A} and Anca Askanase and Thomas Stoll and Bruce, {Ian N} and Jonas Wetter{\"o} and Christopher Sj{\"o}wall",

year = "2020",

month = jan,

doi = "10.1016/j.jaut.2019.102340",

language = "English",

volume = "106",

pages = "102340",

journal = "Journal of Autoimmunity",

issn = "0896-8411",

publisher = "Academic Press",

}

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

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

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U2 - 10.1016/j.jaut.2019.102340

DO - 10.1016/j.jaut.2019.102340

M3 - Journal article

C2 - 31629628

SN - 0896-8411

VL - 106

SP - 102340

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

M1 - 102340

ER -

Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus

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Keywords

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