Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement.
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.
Trysberg
Estelle
E
Department of Rheumatology and Inflammation Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden. Estelle@immuno.gu.se
Blennow
Kaj
K
Zachrisson
Olof
O
Tarkowski
Andrej
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000201:enzymology / Q000473:pathology; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D004790:Enzyme Induction; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D006801:Humans; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000134:cerebrospinal fluid; D007964:Leukocytosis / Q000209:etiology; D008180:Lupus Erythematosus, Systemic / Q000134:cerebrospinal fluid / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000134:cerebrospinal fluid*; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D008582:Meningitis, Aseptic / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000209:etiology; D008875:Middle Aged; D009188:Myelitis, Transverse / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000209:etiology; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D011618:Psychotic Disorders / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000209:etiology; D012640:Seizures / Q000134:cerebrospinal fluid / Q000201:enzymology / Q000209:etiology; D016875:tau Proteins
D002556:Cerebrospinal Fluid Proteins; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D016209:Interleukin-8; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D016875:tau Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9