Abstract
Inflammatory demyelinating disorders of the central nervous system are debilitating conditions of the young adult, here we focus on multiple sclerosis (MS) and neuro-Behçet disease (NBD). MS is an autoimmune disorder of the central nervous system. NBD, a neurological manifestation of an idiopathic chronic relapsing multisystem inflammatory disease, the behçet disease. The diagnosis of MS and NBD relies on clinical symptoms, magnetic resonance imaging and laboratory tests. At first onset, clinical and imaging similarities between the two disorders may occur, making differential diagnosis challenging and delaying appropriate management. Aiming to identify additional discriminating biomarker patterns, we measured and compared gene expression of a broad panel of selected genes in blood and cerebrospinal fluid (CSF) cells of patients suffering from NBD, MS and non inflammatory neurological disorders (NIND). To reach this aim, bivariate and multivariate analysis were applied. The Principal Analysis Component (PCA) highlighted distinct profiles between NBD, MS, and controls. Transcription factors foxp3 in the blood along with IL-4, IL-10, and IL-17 expressions were the parameters that are the main contributor to the segregation between MS and NBD clustering. Moreover, parameters related to cellular activation and inflammatory cytokines within the CSF clearly differentiate between the two inflammatory diseases and the controls. We proceeded to ROC analysis in order to identify the most distinctive parameters between both inflammatory neurological disorders. The latter analysis suggested that IL-17, CD73 in the blood as well as IL-1β and IL-10 in the CSF were the most discriminating parameters between MS and NBD. We conclude that combined multi-dimensional analysis in blood and CSF suggests distinct mechanisms governing the pathophysiology of these two neuro-inflammatory disorders.
Highlights
Multiple sclerosis (MS) and neurological Behçet disease (NBD) are two inflammatory recurrent diseases affecting the central nervous system (CNS)
There was no significant difference in the blood-brain barrier (BBB) disruption among the three groups as demonstrated by the cerebrospinal fluid (CSF) to albumin ratio (Table 1)
We investigated the expression genes related to the major immune axes in blood and CSF compartments of treatment-naive patients suffering from RRMS and NBD
Summary
Multiple sclerosis (MS) and neurological Behçet disease (NBD) are two inflammatory recurrent diseases affecting the central nervous system (CNS). NBD, is associated with an inflammatory cascade and neutrophils’ infiltration in the CSF (Al-Araji and Kidd, 2009; Kalra et al, 2014). These two disorders share the feature of presenting episodes of relapses and remissions (Caruso and Moretti, 2018). Both showed the same encephalomyelopathy, disseminated in time and space (Sefidbakht et al, 2014). Despite these similarities, these two pathologies exhibited different cranial MRI lesions. Epidemiological estimation suggested that MS is more prevalent for women (2:1 to 3:1) (Stadelmann, 2011; Leray et al, 2016), in opposition to NBD that affects men more frequently (Akman-Demir et al, 1999; Ideguchi et al, 2010; Houman et al, 2013; Acar-Özen and Tuncer, 2021)
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