Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a pathological condition characterized by incapacitating fatigue and a combination of neurologic, immunologic, and endocrine symptoms. At present its diagnosis is based exclusively on clinical criteria. Several studies have described altered immunologic profiles; therefore, we proposed to further examine the more significant differences, particularly T and NK cell subpopulations that could be conditioned by viral infections, to discern their utility in improving the diagnosis and characterization of the patients. The study included 76 patients that fulfilled the revised Canadian Consensus Criteria (CCC 2010) for ME/CFS and 73 healthy controls, matched for age and gender. Immunophenotyping of different T cell and natural killer cell subpopulations in peripheral blood was determined by flow cytometry. ME/CFS patients showed significantly lower values of T regulatory cells (CD4+CD25++(high)FOXP3+) and higher NKT-like cells (CD3+CD16+/−CD56+) than the healthy individuals. Regarding NK phenotypes, NKG2C was significantly lower and NKCD69 and NKCD56 bright were significantly higher in the patients group. A classification model was generated using the more relevant cell phenotype differences (NKG2C and T regulatory cells) that was able to classify the individuals as ME/CFS patients or healthy in a 70% of cases. The observed differences in some of the subpopulations of T and NK cells between patients and healthy controls could define a distinct immunological profile that can help in the diagnostic process of ME/CFS patients, contribute to the recognition of the disease and to the search of more specific treatments. However, more studies are needed to corroborate these findings and to contribute to establish a consensus in diagnosis.

Highlights

  • Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a pathological condition characterized by incapacitating fatigue for several months not remitting with rest and a combination of symptoms based on neurologic, immunologic, and endocrine disturbances [1, 2], such as postexertional malaise, pain, unrefreshing sleep, cognitive impairment, orthostatic intolerance, flu-like symptoms, anxiety, and depression, among others

  • The patients were selected among patients with a diagnosis of ME/CFS, members of a group dedicated to the research, diagnosis, and treatment of ME/CFS in Barcelona, Madrid, and San Sebastian (ASSSEMBiomedics), that fulfilled the revised Canadian Consensus Criteria (CCC 2010) assessed by two medical practitioners and following a questionnaire

  • The minimum best model used T regulatory cells and NKG2C with approximately 70% accuracy, i.e., we were able to classify the individuals as ME/CFS patients or healthy with those two attributes in a 70% of cases

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Summary

Introduction

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a pathological condition characterized by incapacitating fatigue for several months not remitting with rest and a combination of symptoms based on neurologic, immunologic, and endocrine disturbances [1, 2], such as postexertional malaise, pain, unrefreshing sleep, cognitive impairment, orthostatic intolerance, flu-like symptoms, anxiety, and depression, among others. It is defined as a neurological disease (ICD G93.3). It is crucial that the diagnosis can be supported on objective tests

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