Background and aims To identify cerebrospinal fluid (CSF) biomarkers for the diagnosis and disease severity evaluation of neuropsychiatric systemic lupus erythematosus (NPSLE).
Methods CSF samples (36 NPSLE, 19 SLE controls, 4 other connective tissue disease controls and 10 other nervous system disease controls) and serum samples (21 NPSLE and 6 SLE controls) were included in this study. The levels of UCH-L1 and its autoantibody were determined by Luminex multiplex (xMAP) assays and enzyme-linked immunosorbent assay (ELISA) respectively.
Results 1) Among 6 candidate neurological disease related proteins, including ubiquitin carboxyl hydrolase L1 (UCH-L1), total Tau protein, phospho-Tau protein, DJ-1 protein, nerve growth factor (NGF) and α-Synuclein (α-SYN), UCH-L1 was significantly elevated in the CSF of patients with NPSLE defined by 2001 Ainiala’s modified criteria, while it was lower in those defined by 1999 ACR criteria but merely presented with headache or mild mood disorder, and in SLE controls whose neuropsychiatric manifestations were not due to SLE. The elevation of CSF UCH-L1 levels were associated with elevated SLEDAI and the number of NPSLE manifestations diagnosed in individual patients. 2) The CSF levels of UCH-L1 autoantibodies were significantly elevated in patients with NPSLE, and showed a sensitivity of 53% and a specificity of 91% for the diagnosis of NPSLE. CSF anti-UCH-L1 levels were associated with organ involvements, and were positively correlated with serum anti-UCH-L1 levels in the NPSLE patients.
Conclusions Anti-UCH-L1 is a promising CSF biomarker for NPSLE diagnosis with high sensitivity and specificity, and CSF levels of UCH-L1 may reflect the severity of NPSLE.
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