Association of T and NK Cell Phenotype With the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

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.

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…Another important function of HLA class I alleles is to serve as ligands for NK cell receptors. Altered numbers and function of NK cells have been reported by several independent researchers in ME/CFS 14,15,40 . The other associated allele, DQB1*03:03, is an HLA class II allele, which is also interesting in regard to the hypothesis of autoimmunity in ME/CFS.…”

Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

“…Baseline T cell proliferation was lower than controls, and post-vaccination proliferation was higher in ME/CFS patients compared to controls, although these findings were not statistically significant. Lower proliferative responses were observed among other ME/CFS patients as well [ 220 ], and decreased cytotoxicity of NK and T cells [ 217 ], as well as increased levels of cytokine producing CD56bright NK cells [ 221 ], have been documented, although findings have not been consistently confirmed between studies.…”

Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

“…Cytokines reported to be altered in abundance include TNF-α, TGF-β, IFN-γ, IL-1α, IL-1β, IL-6, and IL-4 (1,(5)(6)(7)(8)(9)(10). Some studies have also reported differences in the frequency of CD4 + versus CD8 + T cells, Tregs, and/or memory T cells in patients with ME/CFS (10)(11)(12)(13)(14)(15)(16).…”