Cargando…
Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
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 c...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483846/ https://www.ncbi.nlm.nih.gov/pubmed/28694809 http://dx.doi.org/10.3389/fimmu.2017.00723 |
_version_ | 1783245793107378176 |
---|---|
author | Theorell, Jakob Bileviciute-Ljungar, Indre Tesi, Bianca Schlums, Heinrich Johnsgaard, Mette Sophie Asadi-Azarbaijani, Babak Bolle Strand, Elin Bryceson, Yenan T. |
author_facet | Theorell, Jakob Bileviciute-Ljungar, Indre Tesi, Bianca Schlums, Heinrich Johnsgaard, Mette Sophie Asadi-Azarbaijani, Babak Bolle Strand, Elin Bryceson, Yenan T. |
author_sort | Theorell, Jakob |
collection | PubMed |
description | 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 natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed 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. |
format | Online Article Text |
id | pubmed-5483846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54838462017-07-10 Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients Theorell, Jakob Bileviciute-Ljungar, Indre Tesi, Bianca Schlums, Heinrich Johnsgaard, Mette Sophie Asadi-Azarbaijani, Babak Bolle Strand, Elin Bryceson, Yenan T. Front Immunol Immunology 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 natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed 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. Frontiers Media S.A. 2017-06-26 /pmc/articles/PMC5483846/ /pubmed/28694809 http://dx.doi.org/10.3389/fimmu.2017.00723 Text en Copyright © 2017 Theorell, Bileviciute-Ljungar, Tesi, Schlums, Johnsgaard, Asadi-Azarbaijani, Bolle Strand and Bryceson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Theorell, Jakob Bileviciute-Ljungar, Indre Tesi, Bianca Schlums, Heinrich Johnsgaard, Mette Sophie Asadi-Azarbaijani, Babak Bolle Strand, Elin Bryceson, Yenan T. Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients |
title | Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients |
title_full | Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients |
title_fullStr | Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients |
title_full_unstemmed | Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients |
title_short | Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients |
title_sort | unperturbed cytotoxic lymphocyte phenotype and function in myalgic encephalomyelitis/chronic fatigue syndrome patients |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483846/ https://www.ncbi.nlm.nih.gov/pubmed/28694809 http://dx.doi.org/10.3389/fimmu.2017.00723 |
work_keys_str_mv | AT theorelljakob unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients AT bileviciuteljungarindre unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients AT tesibianca unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients AT schlumsheinrich unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients AT johnsgaardmettesophie unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients AT asadiazarbaijanibabak unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients AT bollestrandelin unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients AT brycesonyenant unperturbedcytotoxiclymphocytephenotypeandfunctioninmyalgicencephalomyelitischronicfatiguesyndromepatients |