Association of Hippocampal Atrophy With Cerebrospinal Fluid Antibodies Against the NR2 Subtype of the N‐Methyl‐D‐Aspartate Receptor in Patients With Systemic Lupus Erythematosus and Patients With Primary Sjögren's Syndrome

Abstract

Objective. Cognitive dysfunction is common in both systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS). Antibodies against the NR2 subtype of the N-methyl-D-aspartate receptor (anti-NR2 antibodies) cause hippocampal atrophy and cognitive impairment in mice and have been associated with memory impairment in both patients with SLE and patients with primary SS. In addition, a reduced volume of hippocampal gray matter has been demonstrated in both SLE and primary SS. This study was undertaken to investigate whether there is a connection between the presence of anti-NR2 antibodies and hippocampal atrophy in human diseases.Methods. Fifty patients with SLE and 50 patients with primary SS underwent clinical examination and cerebral magnetic resonance imaging. Anti-NR2 antibodies in cerebrospinal fluid (CSF) were measured, and hippocampal gray matter volumes were compared between patients who were positive for and those who were negative for anti-NR2 antibodies.Results. Patients with anti-NR2 antibodies in CSF had less hippocampal gray matter than patients without these antibodies. No other differences regarding gray matter volumes in other parts of the brain were identified.Conclusion. The present findings indicate that anti-NR2 antibodies in patients with SLE and primary SS cause neuronal death manifested as reduced hippocampal gray matter, as has been previously demonstrated in mice with autoimmune disease.

Evolution, immunity and the emergence of brain superautoantigens

“…Similarly, cognitive dysfunctions along with brain structural alterations, detectable by magnetic resonance imaging (MRI), were reported in up to 65% patients suffering from primary Sjögren’s syndrome 132– 134 . As in SLE patients, a correlation was observed between titers of anti-NR2 antibodies (in the serum or cerebrospinal fluid) and clinical sores of cognitive dysfunction 130, 135 .…”

“…Cognitive clinical signs in SLE are accompanied with high titers of anti-N-methyl-D-aspartate receptor (NMDA; also named NR2 glutamate receptor) and/or anti-ribosomal antibodies 130, 131 . Similarly, cognitive dysfunctions along with brain structural alterations, detectable by magnetic resonance imaging (MRI), were reported in up to 65% patients suffering from primary Sjögren’s syndrome 132– 134 .…”

Migraine in patients with systemic lupus erythematosus is associated with reduced cerebral grey matter volume but not with measures of glial activation or anti‐NR2 or anti‐P antibodies

“…Anti-cardiolipin IgM and IgG and lupus anticoagulant were measured as previously described [3]. Anti-NR2 antibodies in CSF were analyzed by electrochemiluminescence as previously described [16]. Protein S100B was analyzed in CSF with the Human S100B ELISA kit (Abnova, Jhongli City, Taiwan) according to the manufacturer's instructions.…”

Cerebrospinal Fluid in Clinical Neurology

“…In another study, anti NR2 antibodies were detected in CSF of 44 and 82 % of patients with focal and diffuse NPSLE, respectively (Arinuma et al 2008 ). These antibodies are also associated with hippocampal atrophy (Lauvsnes et al 2014 ).…”