Differential Gene Expression Patterns in Blood and Cerebrospinal Fluid of Multiple Sclerosis and Neuro-Behçet Disease

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.

Increased T-bet/GATA-3 and ROR-γt /Foxp3 Ratios in Cerebrospinal Fluid as Potential Criteria for Definite Neuro-Behçet’s Disease

“…We speculate that this IL-10 was not associated with regulatory cells. In line with this observation, a recent report of our team has suggested that this cytokine is elevated in naive treatment NBD patients [ 21 , 43 ]. These data are in accordance with results from Aridogan, et al, who found an increased level of IL-10 in sera of active Behçet’s disease [ 15 ].…”

Alteration of interleukin-10-producing Type 1 regulatory cells in autoimmune diseases

“…A major contribution for IL-10 in controlling MS development has been initially demonstrated in experimental autoimmune encephalomyelitis (EAE) model, a widely used mouse model for MS, where IL-10 knockout mice were shown to develop a more severe disease, whereas IL-10 transgenic mice were completely resistant to disease development [34,35]. In humans, several reports indicated a lower expression of IL-10 in the cerebrospinal fluid and peripheral blood of relapsing MS patients as compared to healthy donors and remitting MS patients [36][37][38] (Fig. 1).…”