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Unperturbed cytotoxic lymphocyte phenotype and function in myalgic encephalomyelitis/chronic fatigue syndrome patients
Jakob Theorell1*, Indre Bileviciute Ljungar2, 3, Bianca Tesi4, 5, Heinrich Schlums1, Mette S. Johnsgaard6, Babak Asadi Azarbaijani7, 8, Elin Bolle Strand7, 9 and Yenan T. Bryceson1, 10*
Received: 15 Dec 2016; Accepted: 08 Jun 2017.
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress.
Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress.
Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear.
Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive NK cell subsets associated with certain viral infections, and compelling links between stress, adrenaline and cytotoxic lymphocyte function, we re-assessed the role of cytotoxic lymphocytes in ME/CFS.
Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls.
Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing or cytokine production.
One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients.
No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed.
In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators.
In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS.
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00723/abstract
Jakob Theorell1*, Indre Bileviciute Ljungar2, 3, Bianca Tesi4, 5, Heinrich Schlums1, Mette S. Johnsgaard6, Babak Asadi Azarbaijani7, 8, Elin Bolle Strand7, 9 and Yenan T. Bryceson1, 10*
- Department of Medicine, Huddinge, Karolinska Institutet, Sweden
- Department of Rehabilitation Medicine, Karolinska Institutet, Sweden
- Department of Clinical Sciences, Danderyd, Karolinska Institutet, Sweden
- Department of Women’s and Children’s Health, Karolinska Institutet, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden
- Klinikk for Alle, Storo, Norway
- Department of Geriatric Medicine, Oslo University, Norway
- VID Specialized University, Norway
- Department of Geriatric Medicine, Oslo University, Norway
- Department of Clinical Science, University of Bergen, Norway
Received: 15 Dec 2016; Accepted: 08 Jun 2017.
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress.
Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress.
Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear.
Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive NK cell subsets associated with certain viral infections, and compelling links between stress, adrenaline and cytotoxic lymphocyte function, we re-assessed the role of cytotoxic lymphocytes in ME/CFS.
Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls.
Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing or cytokine production.
One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients.
No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed.
In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators.
In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS.
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00723/abstract