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.
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.
The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerly, Liverpool, UK; The Institute of Infection and Global Health, West Derby Street, University of Liverpool, UK. Electronic address: benmic@liv.ac.uk.
B D
BD
Michael
L
L
Elsone
M J
MJ
Griffiths
B
B
Faragher
R
R
Borrow
T
T
Solomon
A
A
Jacob
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051401:Aquaporin 4 / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002454:Cell Differentiation; D054413:Chemokine CCL11 / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood; D002633:Chemotaxis; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000378:metabolism; D009471:Neuromyelitis Optica / Q000097:blood* / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood; D010865:Pilot Projects; D055815:Young Adult
D051401:Aquaporin 4; D015415:Biomarkers; C515456:CCL11 protein, human; C066507:CCL4 protein, human; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase
Eosinophil; Multiple sclerosis; Neuromyelitis optica