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.

Nerve Growth Factor Serum Levels Are Associated With Regional Gray Matter Volume Differences in Schizophrenia Patients

“…Another study suggests a contribution of the age-related decline of BDNF serum levels to hippocampal volume as well as memory decline in late adulthood (61). In patients with systemic lupus erythematosus with neuropsychiatric manifestation, immune cell NGF levels were found to be correlated with brain atrophy reflected by lateral ventricle enlargement and thalamic volume loss (62).…”

Depression, anxiety, and sleep quality in childhood onset systemic lupus erythematosus and relationship with brain-derived neurotrophic factor

“…24 In contrast, BDNF within peripheral blood mononuclear cells showed a significant negative correlation with disease activity in NpSLE patients and protective role of the higher BDNF concentrations against disease activity were suggested. 25 In addition, studies had shown a negative correlation between SLEDAI scores and BDNF levels. 28,29 In our study, we did not observe a significant correlation between BDNF levels and SLEDAI score but BDNF levels were lower in patients with SLEDAI score ≥ 1.…”

“…[22][23][24] In contrast, some studies suggested that active SLE patients presented with higher BDNF levels as a compensatory mechanism. 25,26 Ikenouchi et al 27 reported that serum BDNF levels were increased in the presence of severe psychiatric symptoms due to the organic changes in the brain. On the contrary, low BDNF levels in the presence of neuropsychiatric SLE (NpSLE) might be explained by the impairment of neurons and endothelial cells that produce BDNF due to the endothelial and blood-brain barrier dysfunction.…”

Blood levels of brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE): a systematic review and meta-analysis

“…According to Table 1, eight studies published from 2009 to 2021 provided original data on BDNF blood levels in SLE patients and HCs [26][27][28][29][30][31][32][33]. SLE patients were selected based on the ACR criteria.…”

“…SLE patients were selected based on the ACR criteria. Two studies only compared BDNF levels in SLE patients (n = 59) to HCs (n = 64) [27,29]. Meanwhile, six studies gave All but one study [26] used enzyme-linked immunosorbent assay (ELISA) to measure BDNF levels as an analytical procedure.…”