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Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus |
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| Authors: | James A. Varley Magnus Andersson Eleanor Grant Antonio Berretta Michael S. Zandi Vincent Bondet Darragh Duffy David Hunt Fredrik Piehl MD PhD Patrick Waters Sarosh R. Irani |
| Affiliation: | 1. Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK Department of Neurology, John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK;2. Department of Clinical Neuroscience, Centre for Molecular Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden;3. Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK;4. National Hospital for Neurology and Neurosurgery, London, UK;5. Immunobiology of Dendritic Cells, Inserm U1223, Institut Pasteur, Paris, France;6. Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK Centre for Clinical Brain Sciences (CCBS), University of Edinburgh, Edinburgh, UK |
| Abstract: | This study aimed to characterise both neuronal autoantibodies and levels of interferon α, two proposed causative agents in neuropsychiatric systemic lupus erythematosus (NPSLE). Cerebrospinal fluid (CSF) and plasma from 35 patients with systemic lupus erythematosus (SLE; 15 with NPSLE) showed no antibodies against natively expressed N-methyl-D-aspartate receptors (NMDARs), or the surface of live hippocampal neurons. By comparison to controls (n = 104), patients with SLE had antibodies that bound to a peptide representing the extracellular domain of NMDARs (p < 0.0001), however, binding was retained against both rearranged peptides and no peptide (r = 0.85 and r = 0.79, respectively, p < 0.0001). In summary, neuronal-surface reactive antibodies were not detected in NPSLE. Further, while interferon α levels were higher in SLE (p < 0.0001), they lacked specificity for NPSLE. Our findings mandate a search for novel biomarkers in this condition. ANN NEUROL 2020;88:1244–1250 |
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