Open AccessNR2‐reactive antibody decreases cell viability through augmentation of Ca 2+ influx in systemic lupus erythematosus
Author(s) -
Gono Takahisa,
Takarada Takeshi,
Fukumori Ryo,
Kawaguchi Yasushi,
Kaneko Hirotaka,
Hanaoka Masanori,
Katsumata Yasuhiro,
Yoneda Yukio,
Yamanaka Hisashi
Publication year - 2011
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.30616
Subject(s) - antibody , intracellular , viability assay , chemistry , reactive oxygen species , immunology , antibody titer , microbiology and biotechnology , titer , biology , cell , biochemistry
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 NR2‐reactive 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 2+ level. We also investigated the efficacy of zinc as a modulator of the intracellular Ca 2+ 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 = 0.67, P < 0.0001; n = 23), and there was a significant association between the NR2‐reactive antibody titer and the intracellular Ca 2+ level in NR1/NR2a‐transfected HEK 293 cells (R 2 = 0.69, P < 0.0001). Intracellular Ca 2+ levels were significantly higher in cells incubated with IgG derived from NR2‐reactive antibody–positive SLE patients than in those incubated with IgG derived from NR2‐reactive antibody–negative SLE patients ( P = 0.0002). The addition of zinc decreased the intracellular Ca 2+ level in a dose‐dependent manner. NR2‐reactive antibody–positive SLE IgG weakened the efficacy of zinc as a negative modulator of the intracellular Ca 2+ level. Conclusion Our findings indicate that NR2‐reactive antibody decreases cell viability by Ca 2+ influx in SLE through inhibition of the binding capacity of zinc.