Different blood-brain-barrier disruption profiles in multiple sclerosis, neuromyelitis optica spectrum disorders, and neuropsychiatric systemic lupus erythematosus

Abstract

Aim of the study. To assess differences in BBB damage profiles by measuring serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and S100 calcium-binding protein B (S100B) in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd), and neuropsychiatric systemic lupus erythematosus (NPSLE) patients.Clinical rationale for the study. Blood-brain-barrier (BBB) disruption is one of the key pathological processes involved in various demyelinating diseases of the central nervous system (CNS) and is associated with shedding of cell adhesion molecules and S100B into the serum compartment. Therefore, making an assessment of serum levels of the above-mentioned molecules could provide information about disease pathogenesis, severity of BBB disruption, and disease activity.Material and methods. We recruited 42 RRMS, 19 NMOsd and 35 NPSLE patients. Subjects were treated with beta-interferons or glatiramer acetate (RRMS), oral steroids and/or azathioprine (NMOsd, NPSLE), other immunosuppressants (NPSLE), or antimalarials (NPSLE). The clinical condition of the patients was assessed using the Kurtzke Expanded Disability Status Scale for MS and NMOsd, and the Systemic Lupus Erythematosus Disease Activity Index for NPSLE. Serum levels of sVCAM-1, sPECAM-1, sICAM-1 and S100B were determined using enzyme-linked immunosorbent assay (ELISA).Results. We found the lowest levels of sPECAM-1, sICAM-1 and S100B in sera from NMOsd patients. The highest levels of sPE-CAM-1 and sICAM-1 were observed in NPSLE, and in NPSLE and MS, respectively. There were no statistically significant differences in sVCAM-1 levels between the examined groups. In MS and NMOsd, there was a negative correlation between the EDSS score and the following molecules: sPECAM-1, sICAM-1 and S100B.Conclusions and clinical implications. We conclude that there is a different profile of blood-brain-barrier disruption reflected by cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. These molecules could become new biomarkers to be used in CNS demyelinating diseases differential diagnoses and monitoring disease activity, but further studies on larger groups of patients are necessary.

Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

“…BBB dysfunction is an early event in MS, which is followed by immune cell infiltration and the extravasation of plasma proteins. How the BBB contributes to MS pathogenesis and progression is discussed elsewhere [ 46 , 220 , 221 , 222 , 223 ]. Nishihara et al [ 224 ] showed that different Th subsets had comparable migration rates through the BBB in a transwell setup under inflammatory conditions (mediated by TNF- and interferon- ).…”

Efficacy of satralizumab therapy in the treatment of NMOSD

“…Chociaż przeciwciała przeciwko akwaporynie 4 (AQP4-IgG) uznawane są za swoisty marker NMOSD oraz istotny element patogenezy choroby i czynnik predykcyjny, proces diagnostyczny pozostaje trudny, szczególnie w przypadku pacjentów seronegatywnych [11]. Biomarkerem, który może okazać się pomocny w procesie diagnostycznym takich chorych jest miano MOG-Ab (ang.…”

“…acute disseminated encephalomyelitis). Funkcja MOG pozostaje niejasna, podobnie jak to czy MOG-Ab są patogenne, czy wtórne do wcześniejszego stanu zapalnego, niemniej jednak stały się one ważnym markerem w chorobach demielinizacyjnych [9,11].…”

SARS-CoV-2 and the nervous system

“…Passage through the BBB is rigorously restricted through physical (intercellular and adherence junctions) and metabolic barriers [3]. BBB disruption is one of the key pathological processes involved in various diseases of the CNS [4,5]. Proinflammatory cytokines and disease-specific proteins (e.g.…”