Autoantibodies to Predict Neuropsychiatric Events in SLE
Autoantibodies to Predict Neuropsychiatric Events in SLE
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.
Nervous system involvement in systemic lupus erythematosus (SLE) encompasses a variety of neurological and psychiatric features. Using the American College of Rheumatology (ACR) case definitions, the prevalence of neuropsychiatric disease in SLE varies from 21% to 95%, but only 19–38% of events are attributable to lupus. Neuropsychiatric events present or reoccur at any time in the disease course, although the majority occurs around the time of diagnosis of SLE, particularly those attributable to SLE. The identification of biomarkers at the time of diagnosis to quantify the subsequent risk of neuropsychiatric events attributable to systemic lupus erythematosus (NPSLE) would be helpful.
NPSLE is probably mediated by autoantibodies, microvasculopathy and the intracranial production of inflammatory mediators, often in combination. Lupus-related autoantibodies most frequently associated with NPSLE include antiphospholipid antibodies, anti-ribosomal P antibodies and autoantibodies that bind to neuronal antigens such as the N-methyl-d-aspartate glutamate receptor (anti-NR2). Although there is biological plausibility and experimental data to implicate these autoantibodies in the causality of nervous system disease, studies of human SLE have provided inconsistent findings. Limitations of previous studies include their cross-sectional design, inclusion of patients with variable disease duration, and lack of standardisation in both the classification of neuropsychiatric events and the methodology used for autoantibody detection. We have assembled an international, inception cohort of SLE patients to examine the association between a panel of autoantibodies measured within a mean of 6 months of the time of diagnosis and subsequent nervous system events over a mean follow-up of 3.6 years. Attribution models of different stringency were used to distinguish neuropsychiatric events attributed to SLE and non-SLE causes.
Abstract and Introduction
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.
Introduction
Nervous system involvement in systemic lupus erythematosus (SLE) encompasses a variety of neurological and psychiatric features. Using the American College of Rheumatology (ACR) case definitions, the prevalence of neuropsychiatric disease in SLE varies from 21% to 95%, but only 19–38% of events are attributable to lupus. Neuropsychiatric events present or reoccur at any time in the disease course, although the majority occurs around the time of diagnosis of SLE, particularly those attributable to SLE. The identification of biomarkers at the time of diagnosis to quantify the subsequent risk of neuropsychiatric events attributable to systemic lupus erythematosus (NPSLE) would be helpful.
NPSLE is probably mediated by autoantibodies, microvasculopathy and the intracranial production of inflammatory mediators, often in combination. Lupus-related autoantibodies most frequently associated with NPSLE include antiphospholipid antibodies, anti-ribosomal P antibodies and autoantibodies that bind to neuronal antigens such as the N-methyl-d-aspartate glutamate receptor (anti-NR2). Although there is biological plausibility and experimental data to implicate these autoantibodies in the causality of nervous system disease, studies of human SLE have provided inconsistent findings. Limitations of previous studies include their cross-sectional design, inclusion of patients with variable disease duration, and lack of standardisation in both the classification of neuropsychiatric events and the methodology used for autoantibody detection. We have assembled an international, inception cohort of SLE patients to examine the association between a panel of autoantibodies measured within a mean of 6 months of the time of diagnosis and subsequent nervous system events over a mean follow-up of 3.6 years. Attribution models of different stringency were used to distinguish neuropsychiatric events attributed to SLE and non-SLE causes.
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