Association of anti-NR2 and U1RNP antibodies with neurotoxic inflammatory mediators in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus

• Published in: Lupus Vol. 29; no. 13; pp. 1673 - 1682
• Main Authors: Kondo-Ishikawa, Seiko, Fujii, Takao, Ishigooka, Nozomi, Murakami, Kosaku, Nakashima, Ran, Hashimoto, Motomu, Yoshifuji, Hajime, Tanaka, Masao, Ohmura, Koichiro, Mimori, Tsuneyo
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.11.2020; Sage Publications Ltd
• Subjects: Autoantibodies; Blood-brain barrier; Cerebrospinal fluid; Inflammation; Interleukin 6; Interleukin 8; Lupus; Neurological complications; Neurotoxicity; Systemic lupus erythematosus; γ-Interferon; inflammatory mediators; neuropsychiatric manifestations; Systemic lupus erythematosus; autoantibodies; cerebrospinal fluid
• ISSN: 0961-2033; 1477-0962
• DOI: 10.1177/0961203320954918

Background Autoantibodies (auto Abs) and inflammatory mediators (IMs) in cerebrospinal fluid (CSF) may be involved in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). It is suggested that anti-N-methyl D-aspartate receptor NR2 subunit (NR2) Ab can develop NP manifestation after blood–brain barrier (BBB) abruption. We also reported the association between NPSLE and CSF anti-U1RNP Ab. In the present study, combined effects of CSF anti-NR2 and anti-U1RNP Abs on IMs in patients with NPSLE were examined. Methods CSF samples were collected from 69 patients with NPSLE and 13 non-NPSLE controls. CSF anti-NR2 and anti-U1RNP Abs were determined using ELISA. Levels of IL-6, IL-8, and monokine induced by IFN-γ (MIG) in CSF were measured by quantitative multiplex cytokine analysis. Results CSF IL-6 levels were higher in CSF anti-NR2-positive than in CSF anti-NR2-negative patients (p = 0.003) and non-NPSLE controls (p = 0.015) and were positively correlated with anti-NR2 titer (r = 0.42). CSF IL-8 levels were higher in CSF anti-U1RNP-positive than in CSF anti-U1RNP-negative patients (p = 0.041). CSF MIG levels were more elevated in CSF anti-NR2-positive (p = 0.043) and anti-U1RNP-positive patients (p = 0.029) than in non-NPSLE controls. Additionally, in double positive (DP; both anti-NR2 and U1RNP Ab positive) group, CSF IL-6 and MIG levels were significantly higher than in the double negative (DN; both anti-NR2 and U1RNP Ab negative) group. However, combined effect of both Abs on IM elevation and clinical manifestation was not clear. Conclusions CSF anti-NR2 and anti-U1RNP Abs have different effects on the elevation of CSF IM levels in patients with NPSLE. Additional effect of anti-U1RNP Abs on anti-NR2 Ab-mediated NP manifestation, however, was not recognized in our study.