ObjectiveThis study aims to clarify NADPH oxidases (NOX) enzymes role in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and particularly to prospectively assess NOX2 action by measuring specific biomarkers related to oxidization.BackgroundCIDP is an acquired condition affecting the peripheral nervous system, characterized by progressive symmetrical muscle weakness and distal sensory symptoms. Exact process of myelin destruction is unknown, but CIDP is presumably an autoimmune disease with macrophages as primary effectors. Reactive Oxygen Species (ROS) can induce peroxidation potentially injurious to myelin and increased ROS generation has been seen in neurological disorders. Their formation may be catalyzed by NOX, whose role in neurological disorders have been recently demonstrated, principally for phagocytic isoform NOX2.Design/MethodsTo evaluate NOX2 activity, neutrophil and monocyte oxidative burst was measured directly in fresh whole blood using Phagoburst™ assay by flow cytometry. The mean fluorescence intensity (MFI) in response to different stimuli, which lead to produce ROS, corresponds to the GeoMean that represents the percentage of oxidizing cells and their enzymatic activity.Thirty CIDP patients (mean age 61.9±15.9 years) and 30 healthy control subjects (61.2±14.4 years) have been enrolled in the study.ResultsWe found significant differences among the MFI values of tested groups. In particular, comparing the individual measured oxidative values with normal parameters, in CIDP patients we observed higher out-range values in 80% and 66.7% granulocytes and monocytes burst respectively, and only in 23% and 6.7% controls (p=0.001).ConclusionsShort-term immune therapies are effective in CIDP, but clinical and pathological variability accounts for diagnostic problems and up to one third of cases lack of sustained improvement. Our data suggest an involvement of NOX in ROS formation in CIDP patients. This hypothesis needs to be corroborated, by evaluating their role and eventually establishing markers to better identify patients and potentially effective therapies.Study supported by European Community's Framework Programme (FP7/2007-2013) under grant agreement n° 278611
NADPH Oxidases (NOX) Enzymes Induced Oxidative Stress in CIDP Patients
CALVO, Andrea;MARRALI, GIUSEPPE;SALAMONE, PAOLINA;CASALE, Federico;AMOROSO, Antonio;LOPIANO, Leonardo;CHIO', Adriano;COCITO, DARIO
2014-01-01
Abstract
ObjectiveThis study aims to clarify NADPH oxidases (NOX) enzymes role in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and particularly to prospectively assess NOX2 action by measuring specific biomarkers related to oxidization.BackgroundCIDP is an acquired condition affecting the peripheral nervous system, characterized by progressive symmetrical muscle weakness and distal sensory symptoms. Exact process of myelin destruction is unknown, but CIDP is presumably an autoimmune disease with macrophages as primary effectors. Reactive Oxygen Species (ROS) can induce peroxidation potentially injurious to myelin and increased ROS generation has been seen in neurological disorders. Their formation may be catalyzed by NOX, whose role in neurological disorders have been recently demonstrated, principally for phagocytic isoform NOX2.Design/MethodsTo evaluate NOX2 activity, neutrophil and monocyte oxidative burst was measured directly in fresh whole blood using Phagoburst™ assay by flow cytometry. The mean fluorescence intensity (MFI) in response to different stimuli, which lead to produce ROS, corresponds to the GeoMean that represents the percentage of oxidizing cells and their enzymatic activity.Thirty CIDP patients (mean age 61.9±15.9 years) and 30 healthy control subjects (61.2±14.4 years) have been enrolled in the study.ResultsWe found significant differences among the MFI values of tested groups. In particular, comparing the individual measured oxidative values with normal parameters, in CIDP patients we observed higher out-range values in 80% and 66.7% granulocytes and monocytes burst respectively, and only in 23% and 6.7% controls (p=0.001).ConclusionsShort-term immune therapies are effective in CIDP, but clinical and pathological variability accounts for diagnostic problems and up to one third of cases lack of sustained improvement. Our data suggest an involvement of NOX in ROS formation in CIDP patients. This hypothesis needs to be corroborated, by evaluating their role and eventually establishing markers to better identify patients and potentially effective therapies.Study supported by European Community's Framework Programme (FP7/2007-2013) under grant agreement n° 278611
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