NR2-reactive antibody decreases cell viability through augmentation of Ca 2+ influx in systemic lupus erythematosus

Takahisa Gono, Takeshi Takarada, Ryo Fukumori, Yasushi Kawaguchi, Hirotaka Kaneko, Masanori Hanaoka, Yasuhiro Katsumata, Yukio Yoneda, Hisashi Yamanaka

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3952-3959
Number of pages8
JournalArthritis and Rheumatism
Volume63
Issue number12
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Fingerprint

Systemic Lupus Erythematosus
Cell Survival
Antibodies
Zinc
Immunoglobulin G
N-Methyl-D-Aspartate Receptors
HEK293 Cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

NR2-reactive antibody decreases cell viability through augmentation of Ca 2+ influx in systemic lupus erythematosus. / Gono, Takahisa; Takarada, Takeshi; Fukumori, Ryo; Kawaguchi, Yasushi; Kaneko, Hirotaka; Hanaoka, Masanori; Katsumata, Yasuhiro; Yoneda, Yukio; Yamanaka, Hisashi.

In: Arthritis and Rheumatism, Vol. 63, No. 12, 12.2011, p. 3952-3959.

Research output: Contribution to journalArticle

Gono, T, Takarada, T, Fukumori, R, Kawaguchi, Y, Kaneko, H, Hanaoka, M, Katsumata, Y, Yoneda, Y & Yamanaka, H 2011, 'NR2-reactive antibody decreases cell viability through augmentation of Ca 2+ influx in systemic lupus erythematosus', Arthritis and Rheumatism, vol. 63, no. 12, pp. 3952-3959. https://doi.org/10.1002/art.30616
Gono, Takahisa ; Takarada, Takeshi ; Fukumori, Ryo ; Kawaguchi, Yasushi ; Kaneko, Hirotaka ; Hanaoka, Masanori ; Katsumata, Yasuhiro ; Yoneda, Yukio ; Yamanaka, Hisashi. / NR2-reactive antibody decreases cell viability through augmentation of Ca 2+ influx in systemic lupus erythematosus. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 12. pp. 3952-3959.
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AU - Kaneko, Hirotaka

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N2 - 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.

AB - 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.

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