La Neuromielitie ottica (NMO) è una malattia demielinizzante infiammatoria del sistema nervoso centrale (SNC). Si distingue dalla sclerosi multipla (SM) da caratteristiche cliniche radiologiche e dalla presenza di anticorpi acquaporina-4 in circa il 70%. Nonostante la scoperta di questi anticorpi e l'evidenza dei neutrofili e degli eosinofili nel parenchima del SNC, la immunopatogenesi di NMO rimane poco chiara. Sono principalmente stati condotti studi precedenti che tentano di valutare le citochine e chemochine in ruolo nella NMO nel liquido cerebrospinale acuta da gruppi dell'est asiatico, che hanno valutato un piccolo numero di mediatori in isolamento e non hanno rappresentato importanti fattori di confondimento tra cui lo stato anticorpale e la gravità della malattia. Quindi abbiamo condotto uno studio su una gamma più ampia di citochine e mediatori associati nel siero post-acuto da un gruppo del Regno Unito usando le tecniche analitiche non supervisionate e multivariate per valutare la concentrazione relativa di mediatori in concerto. Il nostro studio su 29 pazienti (anticorpo aquaporin -4 positivo NMO n = 19, MS n = 10), abbinati se possibile, anche per la gravità della malattia, ha identificato e confermato alcune citochine / chemochine, indicatori chiave nella neuromielite ottica distinta dalla sclerosi multipla. I nostri risultati mostrano ulteriore l'importanza dei mediatori infiammatori specifici con funzione predominante nella differenziazione, chemiotassi e l'attività dei neutrofili ed eosinofili, in particolare CCL4, CCL11, granulociti fattore stimolante le colonie e la mieloperossidasi, e questi possono rappresentare potenziali bersagli immunomodulatori.
Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system. It is distinguished from multiple sclerosis (MS) by clinical and radiological features and the presence of aquaporin 4 antibodies in approximately 70%. Despite the discovery of these antibodies and the evidence of neutrophils and eosinophils in the CNS parenchyma, the immunopathogenesis of NMO remains poorly understood. Previous studies attempting to assess the role cytokines and chemokines in NMO have primarily been conducted in acute cerebrospinal fluid from East Asian cohorts, have assessed small numbers of mediators in isolation and have not accounted for important confounding factors including antibody status and disease severity. Therefore we conducted a study of a more extensive range of cytokines and associated mediators in post-acute serum from a UK cohort using unsupervised and multivariate analytical techniques to assess the relative concentration of mediators in concert. Our study of 29 patients (aquaporin 4 antibody positive NMO n=19, MS n=10), matched where possible, including for disease severity, has identified and confirmed some key cytokine/chemokine markers in NMO distinct from MS. Our findings shed further light on the importance of specific inflammatory mediators with predominant function in the differentiation, chemotaxis and activity of neutrophils and eosinophils, particularly CCL4, CCL11, granulocyte-colony stimulating factor and myeloperoxidase, and these may represent potential immunomodulatory targets.
Neuromyelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system. It is distinguished from multiple sclerosis (MS) by clinical and radiological features and the presence of aquaporin 4 antibodies in approximately 70%. Despite the discovery of these antibodies and the evidence of neutrophils and eosinophils in the CNS parenchyma, the immunopathogenesis of NMO remains poorly understood. Previous studies attempting to assess the role cytokines and chemokines in NMO have primarily been conducted in acute cerebrospinal fluid from East Asian cohorts, have assessed small numbers of mediators in isolation and have not accounted for important confounding factors including antibody status and disease severity. Therefore we conducted a study of a more extensive range of cytokines and associated mediators in post-acute serum from a UK cohort using unsupervised and multivariate analytical techniques to assess the relative concentration of mediators in concert. Our study of 29 patients (aquaporin 4 antibody positive NMO n=19, MS n=10), matched where possible, including for disease severity, has identified and confirmed some key cytokine/chemokine markers in NMO distinct from MS. Our findings shed further light on the importance of specific inflammatory mediators with predominant function in the differentiation, chemotaxis and activity of neutrophils and eosinophils, particularly CCL4, CCL11, granulocyte-colony stimulating factor and myeloperoxidase, and these may represent potential immunomodulatory targets.
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