Abstract
BackgroundAntibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE). The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE.Methods and FindingsWe analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE), 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI). In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC) was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 × 10−6 mm2/s; p = 0.006 and 949 × 10−6 mm2/s; p = 0.019, respectively) was lower than in healthy control participants (1152 × 10−6 mm2/s). Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 × 10−6 mm2/s) was lower (p = 0.029) than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 × 10−6 mm2/s) and also lower (p = 0.001) than in healthy control participants.ConclusionsThis is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies.
Highlights
The influence of the immune system on cognition and emotion is unclear
Patients with systemic lupus erythematosus (SLE) with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies
The aim of our study was to assess whether the hippocampus and the amygdala are selectively affected in patients with neuropsychiatric SLE (NP-SLE) and SLE, and whether anti-NMDAR antibodies are involved in creating changes in these brain structures
Summary
The influence of the immune system on cognition and emotion is unclear. Recently, it was shown that antibodies could alter emotional behavior in a rodent model of human autoimmune disease, systemic lupus erythematosus (SLE) [1]. The immune system has to respond rapidly to foreign antigens (bits of proteins that are unique to the pathogen) but ignore self-antigens In autoimmune diseases, this ability to discriminate between self and nonself fails for unknown reasons, and the immune system begins to destroy human tissues. Patients with SLE make numerous ‘‘autoantibodies’’ (antibodies are molecules made by the immune system that recognize and attack antigens; autoantibodies attack selfantigens). These autoantibodies start the attack on the body; other parts of the immune system join in, causing inflammation and forming deposits of immune cells, both of which damage tissues. There is no cure for SLE, but mild cases are controlled with ibuprofen and other non-steroidal anti-inflammatory drugs; severe cases are kept in check with corticosteroids and other powerful immunosuppressants
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