Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

J. G. Hanly, M. B. Urowitz, L. Su, S. C. Bae, C. Gordon, A. Clarke, S. Bernatsky, A. Vasudevan, D. Isenberg, A. Rahman, D. J. Wallace, P. R. Fortin, D. Gladman, J. Romero-Dirz, J. Sanchez-Guerrero, M. A. Dooley, I. Bruce, K. Steinsson, M. Khamashta, S. Manzi & 19 others R. Ramsey-Goldman, G. Sturfelt, O. Nived, R. Van Vollenhoven, M. Ramos-Casals, C. Aranow, M. Mackay, K. Kalunian, G. S. Alarcoń, B. J. Fessler, G. Ruiz-Irastorza, Michelle Petri, S. Lim, D. Kamen, C. Peschken, V. Farewell, K. Thompson, C. Theriault, J. T. Merrill

Research output: Contribution to journalArticle

Abstract

Objective: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti- β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results: Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

Original languageEnglish (US)
Pages (from-to)1726-1732
Number of pages7
JournalAnnals of the Rheumatic Diseases
Volume70
Issue number10
DOIs
StatePublished - Oct 2011

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Lupus Coagulation Inhibitor
Biomarkers
Systemic Lupus Erythematosus
Autoantibodies
Glycoproteins
Intracranial Thrombosis
Antibodies
Glutamate Receptors
Psychotic Disorders
Anti-Idiotypic Antibodies
Hazards
Prospective Studies

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Hanly, J. G., Urowitz, M. B., Su, L., Bae, S. C., Gordon, C., Clarke, A., ... Merrill, J. T. (2011). Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. Annals of the Rheumatic Diseases, 70(10), 1726-1732. https://doi.org/10.1136/ard.2010.148502

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. / Hanly, J. G.; Urowitz, M. B.; Su, L.; Bae, S. C.; Gordon, C.; Clarke, A.; Bernatsky, S.; Vasudevan, A.; Isenberg, D.; Rahman, A.; Wallace, D. J.; Fortin, P. R.; Gladman, D.; Romero-Dirz, J.; Sanchez-Guerrero, J.; Dooley, M. A.; Bruce, I.; Steinsson, K.; Khamashta, M.; Manzi, S.; Ramsey-Goldman, R.; Sturfelt, G.; Nived, O.; Van Vollenhoven, R.; Ramos-Casals, M.; Aranow, C.; Mackay, M.; Kalunian, K.; Alarcoń, G. S.; Fessler, B. J.; Ruiz-Irastorza, G.; Petri, Michelle; Lim, S.; Kamen, D.; Peschken, C.; Farewell, V.; Thompson, K.; Theriault, C.; Merrill, J. T.

In: Annals of the Rheumatic Diseases, Vol. 70, No. 10, 10.2011, p. 1726-1732.

Research output: Contribution to journalArticle

Hanly, JG, Urowitz, MB, Su, L, Bae, SC, Gordon, C, Clarke, A, Bernatsky, S, Vasudevan, A, Isenberg, D, Rahman, A, Wallace, DJ, Fortin, PR, Gladman, D, Romero-Dirz, J, Sanchez-Guerrero, J, Dooley, MA, Bruce, I, Steinsson, K, Khamashta, M, Manzi, S, Ramsey-Goldman, R, Sturfelt, G, Nived, O, Van Vollenhoven, R, Ramos-Casals, M, Aranow, C, Mackay, M, Kalunian, K, Alarcoń, GS, Fessler, BJ, Ruiz-Irastorza, G, Petri, M, Lim, S, Kamen, D, Peschken, C, Farewell, V, Thompson, K, Theriault, C & Merrill, JT 2011, 'Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus', Annals of the Rheumatic Diseases, vol. 70, no. 10, pp. 1726-1732. https://doi.org/10.1136/ard.2010.148502
Hanly, J. G. ; Urowitz, M. B. ; Su, L. ; Bae, S. C. ; Gordon, C. ; Clarke, A. ; Bernatsky, S. ; Vasudevan, A. ; Isenberg, D. ; Rahman, A. ; Wallace, D. J. ; Fortin, P. R. ; Gladman, D. ; Romero-Dirz, J. ; Sanchez-Guerrero, J. ; Dooley, M. A. ; Bruce, I. ; Steinsson, K. ; Khamashta, M. ; Manzi, S. ; Ramsey-Goldman, R. ; Sturfelt, G. ; Nived, O. ; Van Vollenhoven, R. ; Ramos-Casals, M. ; Aranow, C. ; Mackay, M. ; Kalunian, K. ; Alarcoń, G. S. ; Fessler, B. J. ; Ruiz-Irastorza, G. ; Petri, Michelle ; Lim, S. ; Kamen, D. ; Peschken, C. ; Farewell, V. ; Thompson, K. ; Theriault, C. ; Merrill, J. T. / Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus. In: Annals of the Rheumatic Diseases. 2011 ; Vol. 70, No. 10. pp. 1726-1732.
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abstract = "Objective: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti- β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results: Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1{\%} female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3{\%}) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4{\%} (model A) and 28.2{\%} (model B). At enrolment 21.9{\%} of patients had LA, 13.4{\%} anticardiolipin, 15.1{\%} anti-β2 glycoprotein-I, 9.2{\%} anti-ribosomal P and 13.7{\%} anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95{\%} CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95{\%} CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.",
author = "Hanly, {J. G.} and Urowitz, {M. B.} and L. Su and Bae, {S. C.} and C. Gordon and A. Clarke and S. Bernatsky and A. Vasudevan and D. Isenberg and A. Rahman and Wallace, {D. J.} and Fortin, {P. R.} and D. Gladman and J. Romero-Dirz and J. Sanchez-Guerrero and Dooley, {M. A.} and I. Bruce and K. Steinsson and M. Khamashta and S. Manzi and R. Ramsey-Goldman and G. Sturfelt and O. Nived and {Van Vollenhoven}, R. and M. Ramos-Casals and C. Aranow and M. Mackay and K. Kalunian and Alarcoń, {G. S.} and Fessler, {B. J.} and G. Ruiz-Irastorza and Michelle Petri and S. Lim and D. Kamen and C. Peschken and V. Farewell and K. Thompson and C. Theriault and Merrill, {J. T.}",
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TY - JOUR

T1 - Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

AU - Hanly, J. G.

AU - Urowitz, M. B.

AU - Su, L.

AU - Bae, S. C.

AU - Gordon, C.

AU - Clarke, A.

AU - Bernatsky, S.

AU - Vasudevan, A.

AU - Isenberg, D.

AU - Rahman, A.

AU - Wallace, D. J.

AU - Fortin, P. R.

AU - Gladman, D.

AU - Romero-Dirz, J.

AU - Sanchez-Guerrero, J.

AU - Dooley, M. A.

AU - Bruce, I.

AU - Steinsson, K.

AU - Khamashta, M.

AU - Manzi, S.

AU - Ramsey-Goldman, R.

AU - Sturfelt, G.

AU - Nived, O.

AU - Van Vollenhoven, R.

AU - Ramos-Casals, M.

AU - Aranow, C.

AU - Mackay, M.

AU - Kalunian, K.

AU - Alarcoń, G. S.

AU - Fessler, B. J.

AU - Ruiz-Irastorza, G.

AU - Petri, Michelle

AU - Lim, S.

AU - Kamen, D.

AU - Peschken, C.

AU - Farewell, V.

AU - Thompson, K.

AU - Theriault, C.

AU - Merrill, J. T.

PY - 2011/10

Y1 - 2011/10

N2 - Objective: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti- β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results: Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

AB - Objective: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti- β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results: Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

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