Background and aims Anti-DNA/NR2 antibodies are a subset of anti DNA autoantibodies that cross-react with the extracellular domain of the GluN2A/GluN2B subunits of the N-methyl-d-aspartate receptor 2 (NR2), which induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric SLE (NPSLE) can develop after initiation of steroid (post-steroid neuropsychiatric manifestation: PSNP) or before treatment (de novo NPSLE). The objective of this study was to clarify the prevalence of anti-DNA/NR2 antibodies in PSNP-SLE and de novo NPSLE

Methods This study involved a cohort of patients with NPSLE who were admitted to Hokkaido University Hospital. NPSLE patients were classified into two groups, de novo NPSLE and PSNP-SLE. Serum anti-DNA antibodies and anti-DNA/NR2 antibodies were measured using in-house ELISAs.

Results Serum samples were obtained from 29 patients with de novo NPSLE, 26 with PSNP-SLE and 83 healthy controls (HC). The levels of anti-DNA antibodies in patients with de novo NPSLE and PSNP-SLE were significantly higher than those in healthy controls (de novo NPSLE, PSNP-SLE, HC: 1.34±0.09, 1.40±0.14, 0.33±0.03, p<0.0001). The levels of anti-DNA/NR2 antibodies were highest in de novo NPSLE and in PSNP-SLE and HC (de novo NPSLE, PSNP-SLE, HC: 0.75±0.10, 0.60±0.07, 0.49±0.03). In PSNP-SLE, the frequency of mood disorders was higher than that in de novo NPSLE (58% vs 31% p<0.05).

Conclusions The levels of anti-DNA/NR2 in PSNP-SLE are lower than in de novo NPSLE, indicating the differences in the pathogenesis of these two conditions.