Session Type: Abstract Submissions (ACR)
Background/Purpose: Approximately 1/5 of all systemic lupus erythematosus (SLE) starts in childhood and central nervous system (CNS) dysfunction is more common in childhood-onset SLE. CNS disease is second only to nephritis as a cause of morbidity and mortality in patients with SLE. Despite these findings, the diagnosis of CNS disease in SLE remains difficult. Anti-NMDA receptor antibodies are anti-double stranded DNA antibodies that cross react with the NMDA receptors NR2a and NR2b. The activation of the NMDA receptor is critical in learning and memory and is expressed on neurons throughout the hippocampus and cortex. The purpose of this study is to measure the prevalence of anti-NR2 glutamate receptor antibodies in patients with childhood onset SLE and JIA and to assess the association between elevated anti-NMDA-NR2 subunit receptor antibodies and neurocognitive dysfunction in pediatric patients with SLE and patients with JIA.
Methods: Patients diagnosed with SLE prior to age 18 were recruited along with a JIA control patient. Each patient underwent formal neurocognitive testing, assessing a range of cognitive domains. Serum NMDA receptor-NR-2 subunit antibody levels were measured in all subjects by ELISA.
Results: 17 lupus patients (16 female, 1 male, 9 African American, 5 Caucasian, 3 others), ages 10-20 and 7 JIA patients (5 female, 2 male, all Caucasian), ages 10-21 completed NMDA receptor antibody testing and of those all but one SLE patient completed formal neurocognitive testing. T-test comparison of the lupus cohort to the JIA cohort revealed that there were group differences for Full Scale IQ (p=.007), single word reading skills (p=.013), and math calculation skills (p=.039). The JIA patients performed better in these areas than did the SLE patients. The SLE patients also had higher NMDA receptor antibody levels and NMDA receptor antibodies correlated significantly (p=.005) with reaction time.
Conclusion: These findings suggest that pediatric patients with lupus have greater cognitive dysfunction than do patients with JIA. Patients with lupus also had higher NMDA receptor antibody levels than did the JIA controls. The higher antibody levels correlated with reaction time which has been a sensitive index of CNS injury in other diseases such as TBI. These preliminary results suggest that checking NMDA receptor antibody levels may be helpful in patients where there is concern for CNS lupus. Further research is necessary to study these antibody levels over time. We are also currently studying these antibody levels in children of mothers with SLE which will provide insight into the effects of fetal exposure during pregnancy.
Supported by NIH grant: 5K12JD055885-04
N. M. Ruth,
M. C. Kral,
T. K. Nowling,
M. H. Passo,
G. S. Gilkeson,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-association-of-n-methyl-d-aspartate-receptor-antibodies-and-neurocognitive-dysfunction-in-pediatric-lupus-patients-and-in-the-offspring-of-adult-patients-with-lupus/