Vated protein kinase [4?]. A recent work also identified an association of immune abnormalities with the severity of ME/CFS symptoms and an altered quality of life [17]. These immunological abnormalities also involve a decreased expression of the T cell activation marker CD26 expressed on peripheral blood mononuclear cells (PBMC) [18]. This observation, together with the reports that CD26-expression is increased in patients with fibromyalgia [19] or a metabolic syndrome [20], indicates that CD26-expression changes are present in some muscular disorders. Besides T-cell activation and inflammation control, CD26 may also be involved in ME/CFS by its endoproteolytic activity that controls the circulating levels of various effectors involved in anxiety, chronic pain and muscle metabolism. Thus, CD26 can influence the mood, pain and muscle components of ME/CFS [21?4]. The decrease in CD26-expression in ME/CFS may also beassociated with an altered redox status [10?4], a relationship being reported between CD26-expression and redox disorders [25, 26]. Seeking help for the diagnosis of ME/CFS, previous get AZD3759 studies have searched for a correlation between symptoms monitored using analogic scales of fatigue and markers, in particular, oxidative stress and immune markers [17, 27?9]. Other studies reported an alteration of the health-related quality-of-life in ME/CFS patients but did not examine the relationship with biological alterations [30?3]. As indicated above, current case definitions of ME/CFS are based on symptoms and do not use biomarkers. This raises the question of whether people with ME/CFS share any biological abnormalities. If they do the physiological and biological abnormalities found in these patients could become diagnostic markers.MethodsPatientsThe protocol was approved by the Ethics Committee of our institution (CPP Sud Mediterran 1) and the study was carried out by the Code of Ethics of the World Medical Association (Declaration of Helsinki). The procedures have been conducted with the adequate understanding and written consent of the subjects (36 ME/CFS patients and 11 age-matched healthy controls). ME/CFS patients (mean age: 41 ? 6 years; mean weight: 66 ? 3 kg; 22 females) were recruited during this three-year long study (2014?016) and satisfied the criteria defined by the Institute of Medicine of the National Academies [2]: (1) severe chronic fatigue for >6 consecutive months (36/36 cases); (2) a worsening of illness following increases in physical or cognitive activity (36/36 cases); (3) impairment of short-term memory or concentration (36/36 cases), (4) myalgia (24/36 cases); (5) unrefreshing sleep (21/36 cases). In most cases, the ME/CFS began suddenly (30/36), often with PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27532042 a “flu-like” illness (28/36). Exclusionary diagnoses are the medical and psychiatric causes of persistent bodily fatigue. The data on ME/CFS patients were compared to those obtained in an age-matched control group of 11 healthy volunteers (age: 48 ?5 years; weight: 71 ?4 kg; 6 females; same socio-economic class). They consulted for a medical check-up and the medical practitioner did not report any symptoms of ME/CFS during the interview. The healthy volunteers underwent a systematic medical examination, including medical history, physical examination, and laboratory testing, which revealed no abnormalities. Median values of weight did not significantly differ between the ME/CFS and control groups. The characteristics of the subjects are collected in Ta.