Increased serum matrix metalloproteinase 9 levels in systemic lupus erythematosus patients with neuropsychiatric manifestations and brain magnetic resonance imaging abnormalities.

Abstract

To evaluate whether serum matrix metalloproteinase 9 (MMP-9) levels are associated with neuropsychiatric manifestations, particularly cognitive dysfunction, as evaluated by neuropsychological testing and brain magnetic resonance imaging (MRI) abnormalities in patients with systemic lupus erythematosus (SLE). MMP-9 determinations were made in 44 patients with SLE and 43 healthy controls who underwent a clinical neurologic and neuropsychological investigation in order to identify neuropsychiatric manifestations. Cerebral MRI scans with volumetric estimation of intracranial cerebrospinal fluid spaces, T1-weighted lesions, and T2-weighted lesions were performed for all subjects. SLE activity was assessed by the European Consensus Lupus Activity Measure (ECLAM) index, and accumulated neuropsychiatric abnormality was assessed by the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index. No significant difference was found in serum MMP-9 levels between the overall group of SLE patients and controls. However, SLE patients who had at least 1 neuropsychiatric manifestation (NPSLE patients) had significantly higher serum MMP-9 concentrations than did SLE patients without neuropsychiatric syndromes (P = 0.009). Among patients with NPSLE, those with cognitive deficits had significantly higher concentrations of serum MMP-9 than did those with normal cognitive function (P = 0.027). Furthermore, serum MMP-9 levels had a significant positive correlation with the volumes of T1-weighted and T2-weighted lesions in the brain MRI (P = 0.031 and P = 0.015, respectively). The concentration of serum MMP-9 correlated significantly with the SLICC index but not with the ECLAM index. Elevated levels of serum MMP-9 in patients with SLE may reflect neuropsychiatric involvement, particularly cognitive dysfunction. The serum MMP-9 concentration may be associated with small- vessel cerebral vasculopathy and increased risk of cerebral ischemic events in patients with SLE.