Post-acute serum eosinophil and neutrophil-associated cytokine/chemokine profile can distinguish between patients with neuromyelitis optica and multiple sclerosis; and identifies potential pathophysiological mechanisms – A pilot study

• Published in: Cytokine (Philadelphia, Pa.) Vol. 64; no. 1; pp. 90 - 96
• Main Authors: Michael, B.D., Elsone, L., Griffiths, M.J., Faragher, B., Borrow, R., Solomon, T., Jacob, A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2013
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; analytical methods; antibodies; Aquaporin 4 - immunology; aquaporins; Biomarkers - blood; blood serum; Cell Differentiation; central nervous system; cerebrospinal fluid; Chemokine CCL11 - blood; Chemokine CCL4 - blood; chemokines; Chemotaxis; disease severity; Eosinophil; eosinophils; Eosinophils - metabolism; Female; Granulocyte-Macrophage Colony-Stimulating Factor - blood; Humans; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - metabolism; myeloperoxidase; Neuromyelitis optica; Neuromyelitis Optica - blood; Neuromyelitis Optica - metabolism; neutrophils; Neutrophils - metabolism; parenchyma; patients; Peroxidase - blood; Pilot Projects; sclerosis; Young Adult; Multiple sclerosis; Neuromyelitis optica; Eosinophil
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2013.07.019

•29 Patients were studied: AQP4 Ab positive NMO (n=19) and MS (n=10).•Higher IL17a (p=0.0005), G-CSF (p=0.051) and CCL4 (p=0.086) in NMO.•IL17a (p=0.008), G-CSF (p<0.01), MPO (p<0.01), CCL4 (p<0.01) identified NMO.•17 Correctly identified NMO, 9 as MS (OR 54, p<0.001); overall 26 (89.7%) correct.•Importance of mediators with predominant function with neutrophils and eosinophils.
Neuromelitis 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.