title: Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients.
abstract: BACKGROUND
  Mast cells (MCs) mediate inflammation through neuropeptides and cytokines, along with histamine and reactive oxygen species (ROS). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an illness characterized by an unexplained disabling fatigue with multiple physiological impairments as well as dysregulated cytokine profiles.
  
  
  OBJECTIVE
  To determine mast cell phenotypes in isolated human PBMCs, in healthy controls and in CFS/ME patients. Second, determine receptor expression of RAGE and its ligand high mobility group box 1 protein (HMGB1).
  
  
  METHODS
  Moderately severe CFS/ME patients (n=12, mean age 39.25 ± SD3.52 years), severe CFS/ME patients (n=6, mean age 43.00 ± SD4.02 years) and healthy controls (n=13, mean age 42.69 ± SD3.87 years) were included in this study. CFS/ME patients were classified according to the 2011 International Consensus Criteria. LSRFortessa X-20 Flow cytometry was used for the identification of phenotypic peripheral mast cell population in PBMCs using an exclusion marker Lin2 cocktail (anti-CD3, anti-CD14, anti-CD19, anti-CD20 and anti-CD56) and inclusion markers (CD117, CD34, FCεRI, chymase, HLA-DR and CD154) following comparative investigation. HMGB1 and soluble RAGE expression in plasma was measured by sandwich ELISA assay.
  
  
  RESULTS
  There was a significant increase in CD117⁺CD34⁺FCεRI-chymase- mast cell populations in moderate and severe CFS/ME patients compared with healthy controls. There was a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cell populations in the severe CFS/ME compared with healthy controls and moderate CFS/ME. There were no significant differences between groups for HMGB1 and sRAGE.
  
  
  CONCLUSIONS
  This preliminary study investigates mast cell phenotypes from PBMCs in healthy controls. We report significant increase of naïve MCs in moderate and severe CFS/ME patients compared with healthy controls. Moreover, a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cells in severe CFS/ME patients. Peripheral MCs may be present in CFS/ME pathology however, further investigation to determine their role is required.
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Thao
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Johnston
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Anu
authors.initials: A
authors.lastname: Chacko
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Damien
authors.initials: D
authors.lastname: Gibson
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Cepon
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Donald
authors.initials: D
authors.lastname: Staines
authors.affiliation: School of Medical Science, Griffith University, Gold Coast, QLD, Australia.|The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD Australia.
authors.forename: Sonya
authors.initials: S
authors.lastname: Marshall-Gradisnik
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D015673:Fatigue Syndrome, Chronic / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood*
chemical_list: C000593871:AGER protein, human; D015703:Antigens, CD; D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products