Objective. Anti-N-methyl-D-aspartate (anti-NMDA) receptor subunit NR2-reactive antibody may play a crucial role in neuronal manifestations of systemic lupus erythematosus (SLE). However, how NR2reactive antibody acts as a critical modulator of the NMDA receptor is unknown. This study was undertaken to investigate the biologic function of NR2-reactive antibody in patients with SLE.
Methods. The study included 14 patients with SLE, 9 of whom had NR2-reactive antibody. We analyzed the effects of NR2-reactive antibody on cell viability and intracellular Ca 2ุ level. We also investigated the efficacy of zinc as a modulator of the intracellular Ca 2ุ level in the presence of NR2-reactive antibody.
Results. There was a significant inverse correlation between the NR2-reactive antibody titer and cell viability (R 2 โซุโฌ 0.67, P < 0.0001; n โซุโฌ 23), and there was a significant association between the NR2-reactive antibody titer and the intracellular Ca 2ุ level in NR1/ NR2a-transfected HEK 293 cells (R 2 โซุโฌ 0.69, P < 0.0001). Intracellular Ca 2ุ levels were significantly higher in cells incubated with IgG derived from NR2reactive antibody-positive SLE patients than in those incubated with IgG derived from NR2-reactive antibody-negative SLE patients (P โซุโฌ 0.0002). The addition of zinc decreased the intracellular Ca 2ุ level in a dose-dependent manner. NR2-reactive antibodypositive SLE IgG weakened the efficacy of zinc as a negative modulator of the intracellular Ca 2ุ level.
Conclusion.
Our findings indicate that NR2reactive antibody decreases cell viability by Ca 2ุ influx in SLE through inhibition of the binding capacity of zinc.