Abstract
Symptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8 – two cytokines that are known to upregulate MMP-9 – both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.
Highlights
Central nervous system (CNS) involvement has been reported to occur in 14–75% of all systemic lupus erythematosus (SLE) patients [1,2,3]
Our results suggest that matrix metalloproteinases (MMPs)-9 but not MMP-2 actively participates in brain destruction in central nervous system (CNS) lupus
Forty-three patients were found to have Neuropsychiatric involvement in SLE (NPSLE), and nine patients either were found to have phospholipid antibody syndrome or met the CNS lupus criteria but were excluded because of non-SLE origin of neurological events
Summary
Central nervous system (CNS) involvement has been reported to occur in 14–75% of all systemic lupus erythematosus (SLE) patients [1,2,3]. CNS lupus can occur at any time during the course of SLE, and its symptoms are diverse. The features of this condition can include seizures, stroke, depression, psychoses and disordered mentation. Neuropsychiatric involvement in SLE (NPSLE) has been shown to predict a high frequency of flares, and it is considered a major cause of long-standing functional impairment as well as a cause of mortality [4]. Over the past decade CNS lupus has been treated with cytotoxic drugs, which improve disease outcome [5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
