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

• Authors: J G Hanly, Dalhousie University; M B Urowitz, University of Toronto; L Su, University of Cambridge; S-C Bae, Hanyang University; C Gordon, University of Birmingham; A Clarke, McGill University; S Bernatsky, McGill University; A Vasudevan, SUNY Downstate; D Isenberg, University College, London; A Rahman, University College, London; D J Wallace, UCLA; P R Fortin, University of Toronto; D Gladman, University of Toronto; J Romero-Diaz, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico; J Sanchez-Guerrero, Instituto Nacional de Ciencias Medicas y Nutrición, Mexico; M A Dooley, University of North Carolina; I Bruce, University of Manchester; K Steinsson, Landspitali University Hospital; M Khamashta, King's College London; S Manzi, University of Pittsburgh; R Ramsey-Goldman, Northwestern University; G Sturfelt, University Hospital Lund; O Nived, University Hospital Lund; R van Vollenhoven, Karolinska Institute; M Ramos-Casals, Servicio Enfermedades Autoinmunes Hospital Clínico y Provincial, Barcelona; C Aranow, Columbia University; M Mackay, Columbia University; K Kalunian, UCSD; G S Alarcón, University of Alabama at Birmingham; B J Fessler, University of Alabama at Birmingham; G Ruiz-Irastorza, University of the Basque Country; M Petri, Johns Hopkins University; Sung Lim, Emory University; D Kamen, Medical University of South Carolina; C Peschken, University of Manitoba; V Farewell, University of Cambridge; K Thompson, Dalhousie University; C Theriault, Dalhousie University; J T Merrill, Oklahoma Medical Research Foundation
• Journal Title: Annals of the Rheumatic Diseases
• Volume: Volume 70, Number 10
• Publisher: BMJ Publishing Group | 2011-10-01, Pages 1726-1732
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1136/ard.2010.148502
• Subjects: Health Sciences, General; Health Sciences, Epidemiology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Rheumatology; RHEUMATOLOGY; RIBOSOMAL-P PROTEIN; INTERNATIONAL INCEPTION COHORT; ANTIPHOSPHOLIPID ANTIBODIES; CLINICAL-SIGNIFICANCE; GLUTAMATE-RECEPTOR; PREVALENCE; ASSOCIATION; DISEASE; PSYCHOSIS; DIAGNOSIS

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.