epidermal-growth-factor and Multiple-Sclerosis--Relapsing-Remitting

Delay in the diagnosis of multiple sclerosis (MS) stems from the lack of specific clinical and analytical markers to assist in the early diagnosis and prediction of progressive course. We propose a decision-tree model that better defines early at onset MS patients and those with the progressive form by analysing a 12-biomarkers panel in serum and CSF samples of patients with MS, other neurological diseases (OND) and healthy contols. Thus, patients at onset of neurological disease were first classified by serum IL-7 levels <141pg/ml (OR=6.51, p<0.001). Combination of IL-7 and CXCL10 indicated risk for a specific MS clinical form, where IL-7<141 and CXCL10<570pg/ml were associated with the highest risk for PP-MS (OR=22, p=0.01). Unexpectedly, both PP-MS and RR-MS patients shared significantly decreased prototypical biomarkers of inflammation and tissue regeneration in CSF than OND suggesting a defective intrinsic immune response playing a role at the beginning of the disease.

Topics: Area Under Curve; Biomarkers; Case-Control Studies; Chemokine CCL11; Chemokine CCL2; Chemokine CCL4; Chemokine CCL5; Chemokine CXCL10; Chemokine CXCL9; Decision Trees; Dipeptidyl Peptidase 4; Early Diagnosis; Epidermal Growth Factor; Fibroblast Growth Factor 2; Hepatocyte Growth Factor; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-7; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Multivariate Analysis; Nervous System Diseases; Prognosis; Risk Assessment

Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.

Topics: Adult; Biomarkers; Case-Control Studies; Chemokine CCL11; Chemokine CCL4; Cohort Studies; Diagnosis, Differential; Epidermal Growth Factor; Female; Hepatocyte Growth Factor; Humans; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Predictive Value of Tests; ROC Curve

We studied the secretion and regulation of epidermal growth factor (EGF) from immune cells of patients with relapsing remitting multiple sclerosis (RR-MS), and the relevance of these levels to neuronal morphology and survival. Our data suggest that the immune-mediated neuronal and oligodendroglial regeneration may be defective by the increased EGF secretion from immune cells of RR-MS patients. We also suggest an increased neurotoxicity of the immune response in RR-MS via high levels of EGF secretion. This is a heretofore unreported aspect of the immune response of patients with RR-MS. Our results may support the inadequate tissue repair that has been observed in MS.

Topics: Adult; Animals; Cells, Cultured; Epidermal Growth Factor; Female; Humans; Immunity, Cellular; Male; Middle Aged; Monocytes; Multiple Sclerosis, Relapsing-Remitting; PC12 Cells; Rats; T-Lymphocyte Subsets; Young Adult