Background Neuropsychiatric (NP) symptoms are a frequent concern of connective tissue disease (CTD) patients. Although the increased levels of several soluble factors in cerebrospinal fluids (CSF) and lupus autoantibodies (auto Abs) from NP systemic lupus erythematosus (NPSLE) patients1,2 have been reported, their association remains unknown.
Objectives To determine an association of serum- and CSF-anti-U1RNP, SS-A/Ro (SSA) and N-methyl-D-aspartate glutamate receptor (NR2) Abs with CSF-soluble factors in CTD patients with NP manifestations.
Methods Serum- and CSF-anti-U1RNP/SSA Abs were examined by RNA-immunoprecipitation assay reported by our group2, and ELISA3 was used for detection of anti-NR2 Abs. IFN-α, IL-8, IP (interferon inducible protein) -10, MCP (monocyte chemoattractant protein) -1, MIG (monokine induced by IFN-γ), RANTES (regulated upon activation normal T cell expressed and secreted), and fractalkine in the same CSF samples were determined by Procarta® Cytokine Assay kit with Bio-PlexTM.
Results Eighty-two patients with CTD and NP manifestations (76 of SLE, 3 of mixed connective tissue disease, and 3 of Sjögren’s syndrome) were enrolled. Anti-U1RNP Abs were found in sera from 48 (59%) and in CSF from 15 (18%) patients. CSF-anti-U1RNP Abs were never recognized in serum-anti-U1RNP Ab-negative patients. Among 48 patients with serum-anti-U1RNP Abs, CSF-IFN-α (13.7 vs. 4.9 pg/mL, p<0.05) and MCP-1 (364 vs. 208 pg/mL, p<0.05) levels were higher in patients with (=15/48, 31%) than without CSF-anti-U1RNP Abs (=33/48, 69%). No significant difference of soluble factor concentrations, however, was recognized between CSF-anti-U1RNP Ab-positive (15/82, 18%) and -negative (67/82, 82%) including serum-anti-U1RNP-negative patients. Whereas CSF-anti-NR2 Abs were often detected also in serum-anti-NR2 Ab-negative patients, CSF-MIG level was higher in CSF-anti-NR2 Ab-positive (25/82, 30%) than in –negative (57/82, 70%) patients (3499 vs. 153 pg/mL, p<0.05). Anti-U1RNP Ab- and NR2 Ab-positivity in CSF were not correlated. CSF-anti-SSA Abs were detected only in 4 patients and not associated with any soluble factors. There was no association between serum-auto Abs and CSF-soluble factors. In serum-anti-U1RNP Ab- or CSF-anti-NR2 Ab-positive patients, IgG index was higher compared with that in –negative patients (0.69 vs. 0.52 for serum-anti-U1RNP Abs, and 0.73 vs. 0.57 for CSF-anti-NR2 Abs, p<0.05).
Conclusions CSF-anti-U1RNP and NR2 Abs were associated with different subset of soluble factors in CSF, which may have a pathogenic role in NPSLE. Additionally, anti-U1RNP Abs in serum appeared to be involved in the increased levels of CSF-IFN-α and MCP-1 in NPSLE patients with CSF-anti-U1RNP Abs.
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Disclosure of Interest None Declared