Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients.

ABSTRACT

OBJECTIVE: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE. METHODS: Selected neurotrophins (BDNF, NGF, NT-3, and NT-4/5) were measured with ELISA within peripheral blood mononuclear cells (PBMCs) isolated from 38 NPSLE patients matched with 39 healthy controls. Subcortical and cortical structure volumes were segmented with the Freesurfer 5.3 pipeline on T1-weighted isotropic images acquired on a 1.5-T MRI scanner. RESULTS: BDNF and NGF levels in PBMCs were reduced in NPSLE compared to the healthy population. The PBMC BDNF level was associated with reduced thalamus, caudate, and putamen volumes. The NGF level correlated with lateral ventricles enlargement and thalamic volume loss. CONCLUSIONS: In NPSLE, immune cell BDNF and NGF levels are linked with subcortical atrophy. Higher BDNF levels are associated with higher midsagittal atrophy, which may reflect compensatory mechanisms, upregulating BDNF when neuroprotection is needed. These data require further confirmation.