NR2 antibodies in neuropsychiatric systemic lupus erythematosus.

Abstract

NR2 antibodies in neuropsychiatric systemic lupus erythematosus This editorial refers to 'Anti-NR2A antibody as a predictor for neuropsychiatric systemic lupus erythe-matosus', by Takahisa Gono et al., doi:10.1093/ rheumatology/keq408, on page 1578. In the past few decades, patients with SLE have experienced increased longevity in part due to earlier diagnosis and treatment. However, late sequelae have gained increased attention in special cardiovascular disease and cognitive impairment [1]. The prevalence of neuropsychiatric (NP) manifestations ranges between 17 and 75%, reflecting different methods of patient selection and assessment, varying expertise of the assessors and lack of a consensus for diagnosing active and chronic NP symptoms [2]. Clinical symptoms arise from CNS and peripheral nervous system dysfunction and vary from overt neurological and psychiatric disorders to more subtle signs and symptoms such as headache, mood disorders and impairment of cognitive function [2]. In 40% of cases secondary insults, such as infections, metabolic derangement or side effects of drugs may be identified as possible aetiological factors [3]. However, in 60% of the patients NP manifestations are considered primary and pathogenesis of these focal or diffuse manifestations are now being elucidated [1, 2]. One growing interest is the identification of a subset of anti-DNA antibodies that cross-reacts with a consensus pentapeptide present in the NR2A and NR2B subunits of the N-methyl-D-aspartate receptor (NMDAR) [1]. NMDARs are receptors for the neurotransmitter glutamate, the major excitatory neurotransmitter in the brain, which is critically important for many brain functions [1]. Excessive exposure to glutamate results in increased calcium influx that causes mitochondrial stress and activates caspase cascades, leading to neuronal death [1, 4]. Neuronal death leads to reduced tissue volume, visualized on MRI as atrophy [5, 6]. Systematic MRI studies have shown that atrophy, although frequently found in SLE patients , is not uniformly present [6]. The fact that NMDARs are differentially expressed regionally in the brain may be one explanation [1]. Receptors containing NR2A and NR2B are most dense on neurons in the CA1 region of the hippocampus, and in the amygdala: hence, the strong interest in the association of these antibodies with cogni-tive impairment and hippocampal volume [1, 5–7]. In the first part of the study by Gono et al. [8], in this issue, the authors compare two different types of peptide, ISVSYDDWDYSLE and DWEYSVWLSN, as autoantigens to detect anti-NR2A autoantibodies. The median anti-NR2A antibody optic density (OD) value was significantly higher and the range more broad …

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