title: Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers.
abstract: BACKGROUND
  There is now evidence that specific subgroups of patients with Myalgic Encephalomyelitis / chronic fatigue syndrome (ME/CFS) suffer from a neuro-psychiatric-immune disorder. This study was carried out to delineate the expression of the activation markers CD38 and human leukocyte antigen (HLA) DR on CD4+ and CD8+ peripheral blood lymphocytes in ME/CFS.
  
  
  METHODS
  Proportions and absolute numbers of peripheral lymphocytes expressing CD3+, CD19+, CD4+, CD8+, CD38+ and HLA-DR+ were measured in ME/CFS (n=139), chronic fatigue (CF, n=65) and normal controls (n=40).
  
  
  RESULTS
  The proportions of CD3+, CD8+, CD8+CD38+ and CD8+HLA-DR+ were significantly higher in ME/CFS patients than controls, while CD38+, CD8+CD38+, CD8+HLA-DR+ and CD38+HLA-DR+ were significantly higher in ME/CFS than CF. The percentage of CD19+ cells and the CD4+/CD8+ ratio were significantly lower in ME/CFS and CF than in controls. There were highly significant inverse correlations between the increased expression of CD38+, especially that of CD8+CD38+, and the lowered CD4+/CD8+ ratio and CD19+ expression. There were no significant associations between the flow cytometric results and severity or duration of illness and peripheral blood biomarkers of oxidative and nitrosative stress (O&NS, i.e. IgM responses to O&N modified epitopes), leaky gut (IgM or IgA responses to LPS of gut commensal bacteria), cytokines (interleukin-1, tumor necrosis factor-α), neopterin, lysozyme and autoimmune responses to serotonin.
  
  
  CONCLUSIONS
  The results support that a) increased CD38 and HLA-DR expression on CD8+ T cells are biomarkers of ME/CFS; b) increased CD38 antigen expression may contribute to suppression of the CD4+/CD8+ ratio and CD19+ expression; c) there are different immune subgroups of ME/CFS patients, e.g. increased CD8+ activation marker expression versus inflammation or O&NS processes; and d) viral infections or reactivation may play a role in a some ME/CFS patients.
authors.affiliation: IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: AML Laboratories, Antwerp, Belgium.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bosmans
authors.affiliation: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kubera
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015673:Fatigue Syndrome, Chronic / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000276:immunology; D019798:Neopterin / Q000276:immunology; D015538:Nitrosation / Q000276:immunology; D018384:Oxidative Stress / Q000276:immunology; D010539:Permeability; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D015415:Biomarkers; D006684:HLA-DR Antigens; D007375:Interleukin-1; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019798:Neopterin; D009113:Muramidase; D051997:ADP-ribosyl Cyclase 1