PMID- 26707044 OWN - NLM STAT- MEDLINE DCOM- 20160421 LR - 20181202 IS - 0172-780X (Print) IS - 0172-780X (Linking) VI - 36 IP - 5 DP - 2015 TI - 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. PG - 439-46 AB - 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-alpha), 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. FAU - Maes, Michael AU - Maes M AD - IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia. FAU - Bosmans, Eugene AU - Bosmans E AD - AML Laboratories, Antwerp, Belgium. FAU - Kubera, Marta AU - Kubera M AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland. LA - eng PT - Journal Article PL - Sweden TA - Neuro Endocrinol Lett JT - Neuro endocrinology letters JID - 8008373 RN - 0 (Antigens, CD19) RN - 0 (Biomarkers) RN - 0 (HLA-DR Antigens) RN - 0 (Interleukin-1) RN - 0 (TNF protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 670-65-5 (Neopterin) RN - EC 3.2.1.17 (Muramidase) RN - EC 3.2.2.6 (ADP-ribosyl Cyclase 1) SB - IM MH - ADP-ribosyl Cyclase 1/*immunology MH - Adult MH - Antigens, CD19/immunology MH - Biomarkers MH - CD4-CD8 Ratio MH - CD8-Positive T-Lymphocytes/*immunology MH - Fatigue Syndrome, Chronic/*immunology MH - Female MH - HLA-DR Antigens/*immunology MH - Humans MH - Interleukin-1/immunology MH - Intestinal Mucosa/metabolism MH - Intestines/immunology MH - Male MH - Middle Aged MH - Muramidase/immunology MH - Neopterin/immunology MH - Nitrosation/immunology MH - Oxidative Stress/immunology MH - Permeability MH - Tumor Necrosis Factor-alpha/immunology EDAT- 2015/12/29 06:00 MHDA- 2016/04/22 06:00 CRDT- 2015/12/29 06:00 PHST- 2015/08/12 00:00 [received] PHST- 2015/09/03 00:00 [accepted] PHST- 2015/12/29 06:00 [entrez] PHST- 2015/12/29 06:00 [pubmed] PHST- 2016/04/22 06:00 [medline] AID - NEL360515A05 [pii] PST - ppublish SO - Neuro Endocrinol Lett. 2015;36(5):439-46.