ABSTRACT
BACKGROUND: Neuropsychiatric manifestations (NP) are common in systemic lupus erythematosus (SLE). However, the pathophysiological mechanisms are not completely understood. Neurofilament light protein (NfL) is part of the neuronal cytoskeleton. Increased NfL concentrations, reflecting neurodegeneration, is observed in cerebrospinal fluid (CSF) in several neurodegenerative and neuroinflammatory conditions. We aimed to explore if plasma NfL could serve as a biomarker for central nervous system (CNS) involvement in SLE. METHODS: Sixty-seven patients with SLE underwent neurological examination; 52 underwent lumbar puncture, while 62 underwent cerebral magnetic resonance imaging (MRI). We measured selected auto-antibodies and other laboratory variables postulated to have roles in NP pathophysiology in the blood and/or CSF. We used SPM12 software for MRI voxel-based morphometry. RESULTS: Age-adjusted linear regression analyses revealed increased plasma NfL concentrations with increasing creatinine (ß = 0.01, p < 0.001) and Q-albumin (ß = 0.07, p = 0.008). We observed higher plasma NfL concentrations in patients with a history of seizures (ß = 0.57, p = 0.014), impaired motor function (ß = 0.36, p = 0.008), increasing disease activity (ß = 0.04, p = 0.008), and organ damage (ß = 0.10, p = 0.002). Voxel-based morphometry suggested an association between increasing plasma NfL concentrations and the loss of cerebral white matter in the corpus callosum and hippocampal gray matter. CONCLUSION: Increased plasma NfL concentrations were associated with some abnormal neurological, cognitive, and neuroimaging findings. However, plasma NfL was also influenced by other factors, such as damage accrual, creatinine, and Q-albumin, thereby obscuring the interpretation of how plasma NfL reflects CNS involvement. Taken together, NfL in CSF seems a better marker of neuronal injury than plasma NfL in patients with SLE.
Subject(s)
Central Nervous System , Lupus Erythematosus, Systemic , Neurofilament Proteins , White Matter , Albumins , Biomarkers/blood , Central Nervous System/physiopathology , Creatinine , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Neurofilament Proteins/blood , Neurofilament Proteins/cerebrospinal fluidABSTRACT
A severe and persistent migrainous headache in a patient with primary Sjøgren's syndrome unresponsive to treatment with immunosuppressive drugs, triptans, opioids, and NSAIDs, responded successfully to intrathecal B-cell depletion with rituximab. We hypothesize that brain-resident autoreactive B cells were involved in headache pathogenesis and were eliminated by this procedure.
