Association of anti-NR2 and U1RNP antibodies with neurotoxic inflammatory mediators in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus.
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.
['Kondo-Ishikawa|Seiko|S|https://orcid.org/0000-0003-3146-7140', 'Fujii|Takao|T|', 'Ishigooka|Nozomi|N|', 'Murakami|Kosaku|K|', 'Nakashima|Ran|R|', 'Hashimoto|Motomu|M|', 'Yoshifuji|Hajime|H|', 'Tanaka|Masao|M|', 'Ohmura|Koichiro|K|', 'Mimori|Tsuneyo|T|']
D000328:Adult D001323:Autoantibodies D016022:Case-Control Studies D005260:Female D006801:Humans D007249:Inflammation D018836:Inflammation Mediators D020945:Lupus Vasculitis, Central Nervous System D008297:Male D008875:Middle Aged D016194:Receptors, N-Methyl-D-Aspartate D017412:Ribonucleoprotein, U1 Small Nuclear D055815:Young Adult
inflammatory mediators cerebrospinal fluid Systemic lupus erythematosus autoantibodies neuropsychiatric manifestations