Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.
Biomarker
Chronic fatigue syndrome
Diagnostic test
Myalgic encephalomyelitis
Journal
BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723
Informations de publication
Date de publication:
24 05 2023
24 05 2023
Historique:
received:
04
02
2023
accepted:
09
05
2023
medline:
26
5
2023
pubmed:
25
5
2023
entrez:
24
5
2023
Statut:
epublish
Résumé
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted condition that affects most body systems. There is currently no known diagnostic biomarker; instead, diagnosis is dependent on application of symptom-based case criteria following exclusion of any other potential medical conditions. While there are some studies that report potential biomarkers for ME/CFS, their efficacy has not been validated. The aim of this systematic review is to collate and appraise literature pertaining to a potential biomarker(s) which may effectively differentiate ME/CFS patients from healthy controls. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane review guidelines. PubMed, Embase and Scopus were systematically searched for articles containing "biomarker" and "ME/CFS" keywords in the abstract or title and if they included the following criteria: (1) were observational studies published between December 1994 and April 2022; (2) involved adult human participants; (3) full text is available in English (4) original research; (5) diagnosis of ME/CFS patients made according to the Fukuda criteria (1994), Canadian Consensus Criteria (2003), International Consensus Criteria (2011) or Institute of Medicine Criteria (2015); (6) study investigated potential biomarkers of ME/CFS compared to healthy controls. Quality and Bias were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. A total of 101 publications were included in this systematic review. Potential biomarkers ranged from genetic/epigenetic (19.8%), immunological (29.7%), metabolomics/mitochondrial/microbiome (14.85%), endovascular/circulatory (17.82%), neurological (7.92%), ion channel (8.91%) and physical dysfunction biomarkers (8.91%). Most of the potential biomarkers reported were blood-based (79.2%). Use of lymphocytes as a model to investigate ME/CFS pathology was prominent among immune-based biomarkers. Most biomarkers had secondary (43.56%) or tertiary (54.47%) selectivity, which is the ability for the biomarker to identify a disease-causing agent, and a moderate (59.40%) to complex (39.60%) ease-of-detection, including the requirement of specialised equipment. All potential ME/CFS biomarkers differed in efficiency, quality, and translatability as a diagnostic marker. Reproducibility of findings between the included publications were limited, however, several studies validated the involvement of immune dysfunction in the pathology of ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of illness. The heterogeneity shown across many of the included studies highlights the need for multidisciplinary research and uniform protocols in ME/CFS biomarker research.
Sections du résumé
BACKGROUND
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifaceted condition that affects most body systems. There is currently no known diagnostic biomarker; instead, diagnosis is dependent on application of symptom-based case criteria following exclusion of any other potential medical conditions. While there are some studies that report potential biomarkers for ME/CFS, their efficacy has not been validated. The aim of this systematic review is to collate and appraise literature pertaining to a potential biomarker(s) which may effectively differentiate ME/CFS patients from healthy controls.
METHODS
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane review guidelines. PubMed, Embase and Scopus were systematically searched for articles containing "biomarker" and "ME/CFS" keywords in the abstract or title and if they included the following criteria: (1) were observational studies published between December 1994 and April 2022; (2) involved adult human participants; (3) full text is available in English (4) original research; (5) diagnosis of ME/CFS patients made according to the Fukuda criteria (1994), Canadian Consensus Criteria (2003), International Consensus Criteria (2011) or Institute of Medicine Criteria (2015); (6) study investigated potential biomarkers of ME/CFS compared to healthy controls. Quality and Bias were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.
RESULTS
A total of 101 publications were included in this systematic review. Potential biomarkers ranged from genetic/epigenetic (19.8%), immunological (29.7%), metabolomics/mitochondrial/microbiome (14.85%), endovascular/circulatory (17.82%), neurological (7.92%), ion channel (8.91%) and physical dysfunction biomarkers (8.91%). Most of the potential biomarkers reported were blood-based (79.2%). Use of lymphocytes as a model to investigate ME/CFS pathology was prominent among immune-based biomarkers. Most biomarkers had secondary (43.56%) or tertiary (54.47%) selectivity, which is the ability for the biomarker to identify a disease-causing agent, and a moderate (59.40%) to complex (39.60%) ease-of-detection, including the requirement of specialised equipment.
CONCLUSIONS
All potential ME/CFS biomarkers differed in efficiency, quality, and translatability as a diagnostic marker. Reproducibility of findings between the included publications were limited, however, several studies validated the involvement of immune dysfunction in the pathology of ME/CFS and the use of lymphocytes as a model to investigate the pathomechanism of illness. The heterogeneity shown across many of the included studies highlights the need for multidisciplinary research and uniform protocols in ME/CFS biomarker research.
Identifiants
pubmed: 37226227
doi: 10.1186/s12916-023-02893-9
pii: 10.1186/s12916-023-02893-9
pmc: PMC10206551
doi:
Substances chimiques
Biomarkers
0
Types de publication
Systematic Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
189Informations de copyright
© 2023. The Author(s).
Références
J Transl Med. 2020 Jan 6;18(1):4
pubmed: 31906988
Appl Clin Genet. 2016 Mar 31;9:39-47
pubmed: 27099524
Metabolites. 2018 Dec 06;8(4):
pubmed: 30563204
J Transl Med. 2022 Feb 16;20(1):94
pubmed: 35172836
Proc Natl Acad Sci U S A. 2019 May 21;116(21):10250-10257
pubmed: 31036648
Front Neurol. 2018 Nov 27;9:992
pubmed: 30538664
Fatigue. 2017;5(1):15-20
pubmed: 29308330
Front Immunol. 2022 Mar 04;13:841910
pubmed: 35309313
Front Physiol. 2013 May 30;4:119
pubmed: 23755016
J Transl Med. 2020 Jul 29;18(1):290
pubmed: 32727475
J Transl Med. 2020 Feb 24;18(1):100
pubmed: 32093722
Biomolecules. 2021 Aug 11;11(8):
pubmed: 34439855
Expert Rev Mol Diagn. 2018 Jan;18(1):19-26
pubmed: 29200322
Front Public Health. 2020 Aug 21;8:420
pubmed: 32974259
PLoS One. 2016 Mar 11;11(3):e0150904
pubmed: 26967895
Clin Invest Med. 2008 Dec 01;31(6):E319-27
pubmed: 19032901
JIMD Rep. 2016;26:103-13
pubmed: 26354038
Neuro Endocrinol Lett. 2005 Oct;26(5):487-92
pubmed: 16264414
J Transl Med. 2011 May 28;9:81
pubmed: 21619669
Clin Exp Immunol. 2017 Feb;187(2):284-293
pubmed: 27727448
Sci Rep. 2020 Nov 12;10(1):19620
pubmed: 33184353
Int J Mol Sci. 2020 Feb 08;21(3):
pubmed: 32046336
J Intern Med. 2012 Jan;271(1):64-81
pubmed: 21615807
QJM. 2012 Sep;105(9):831-8
pubmed: 22670061
Mol Neurobiol. 2019 Jun;56(6):4249-4257
pubmed: 30298340
J Transl Med. 2022 Mar 22;20(1):138
pubmed: 35317812
BMC Immunol. 2015 Jun 02;16:35
pubmed: 26032326
J Autoimmune Dis. 2005 May 25;2:5
pubmed: 15916704
JBI Evid Synth. 2023 Mar 01;21(3):478-493
pubmed: 36121230
Eur J Neurosci. 2021 Sep;54(6):6214-6228
pubmed: 34355438
Front Immunol. 2019 Apr 16;10:796
pubmed: 31057538
Clin Diagn Lab Immunol. 2003 Mar;10(2):315-6
pubmed: 12626460
Mol Neurobiol. 2018 Jan;55(1):633-641
pubmed: 27981498
BMJ. 2021 Mar 29;372:n71
pubmed: 33782057
BMC Med Genomics. 2017 Feb 23;10(1):11
pubmed: 28231836
J Transl Med. 2013 Apr 09;11:93
pubmed: 23570606
Dyn Med. 2007 Jan 30;6:2
pubmed: 17263876
PLoS One. 2015 Dec 18;10(12):e0145453
pubmed: 26683192
Work. 2020;66(2):327-337
pubmed: 32568152
BMC Infect Dis. 2012 Oct 14;12:258
pubmed: 23061432
Transl Psychiatry. 2016 Sep 27;6(9):e904
pubmed: 27676445
Phys Ther. 2013 Nov;93(11):1484-92
pubmed: 23813081
Sci Rep. 2021 Feb 25;11(1):4541
pubmed: 33633136
J Transl Med. 2019 Dec 4;17(1):409
pubmed: 31801546
J Intern Med. 2010 Apr;267(4):418-35
pubmed: 20433584
J Transl Med. 2019 Mar 14;17(1):80
pubmed: 30871578
BMC Neurol. 2010 Aug 23;10:73
pubmed: 20731841
Clin Exp Immunol. 2005 Dec;142(3):505-11
pubmed: 16297163
Mol Med. 2008 Sep-Oct;14(9-10):599-607
pubmed: 18596870
Cytokine. 2016 Feb;78:27-36
pubmed: 26615570
Behav Brain Funct. 2010 Dec 29;6:76
pubmed: 21190576
Microbiome. 2017 Apr 26;5(1):44
pubmed: 28441964
PLoS One. 2014 Sep 19;9(9):e102783
pubmed: 25238588
Radiology. 2015 Feb;274(2):517-26
pubmed: 25353054
NeuroRx. 2004 Apr;1(2):182-8
pubmed: 15717018
Biomark Res. 2021 Mar 12;9(1):18
pubmed: 33712063
J Med Virol. 2017 Sep;89(9):1636-1645
pubmed: 28303641
NMR Biomed. 2009 Apr;22(3):251-8
pubmed: 18942064
Med Sci Monit. 2011 Apr;17(4):SC11-5
pubmed: 21455120
J Transl Med. 2016 Aug 31;14:251
pubmed: 27580693
Ann Intern Med. 1994 Dec 15;121(12):953-9
pubmed: 7978722
Int J Mol Sci. 2020 Sep 01;21(17):
pubmed: 32883007
Front Immunol. 2017 Jun 26;8:723
pubmed: 28694809
Sci Rep. 2018 Jul 3;8(1):10056
pubmed: 29968805
Sci Rep. 2020 Nov 16;10(1):19933
pubmed: 33199820
Front Comput Neurosci. 2020 Jan 29;14:2
pubmed: 32063839
Sci Adv. 2015 Feb;1(1):
pubmed: 26079000
Sci Rep. 2021 May 19;11(1):10604
pubmed: 34011981
J Natl Cancer Inst. 2009 Nov 4;101(21):1453-63
pubmed: 19855077
FASEB J. 2014 Mar;28(3):1317-30
pubmed: 24327606
J Transl Med. 2017 Mar 16;15(1):60
pubmed: 28302133
Brain Behav Immun Health. 2020 Mar 28;4:100067
pubmed: 34589849
Diagnostics (Basel). 2019 Jul 19;9(3):
pubmed: 31331036
Diagnostics (Basel). 2019 Apr 10;9(2):
pubmed: 30974900
Front Pediatr. 2019 Feb 05;7:12
pubmed: 30805319
Arthritis Care Res (Hoboken). 2016 Jan;68(1):132-40
pubmed: 26097208
J Transl Med. 2021 Aug 28;19(1):370
pubmed: 34454515
Dialogues Clin Neurosci. 2016 Sep;18(3):299-312
pubmed: 27757064
J Intern Med. 2011 Oct;270(4):327-38
pubmed: 21777306
Front Immunol. 2021 Apr 06;12:644548
pubmed: 33889154
Sci Rep. 2020 Feb 7;10(1):2064
pubmed: 32034172
Syst Rev. 2019 Nov 14;8(1):279
pubmed: 31727160
Acta Neurol Scand Suppl. 2007;187:7-14
pubmed: 17419822
J Transl Med. 2009 Nov 12;7:96
pubmed: 19909538
J Allergy Clin Immunol. 2003 Aug;112(2):397-403
pubmed: 12897748
Front Med (Lausanne). 2021 Mar 22;8:642710
pubmed: 33829023
Cell Mol Immunol. 2022 Feb;19(2):127-129
pubmed: 35022604
J Transl Med. 2020 Sep 24;18(1):365
pubmed: 32972442
Mol Biosyst. 2017 Jan 31;13(2):371-379
pubmed: 28059425
J Int Med Res. 2016 Dec;44(6):1381-1394
pubmed: 27834303
J Extracell Vesicles. 2018 Mar 22;7(1):1453730
pubmed: 29696075
Syst Rev. 2016 Dec 5;5(1):210
pubmed: 27919275
BMC Neurol. 2004 Oct 04;4(1):14
pubmed: 15461817
Neuro Endocrinol Lett. 2015;36(5):439-46
pubmed: 26707044
J Immunol Methods. 2014 Apr;406:1-9
pubmed: 24561308
J Pain. 2009 Oct;10(10):1099-112
pubmed: 19647494
BMC Med Genomics. 2009 Jun 25;2:38
pubmed: 19555476
PLoS One. 2010 May 25;5(5):e10817
pubmed: 20520837
Antioxid Redox Signal. 2021 Jun 20;34(18):1420-1427
pubmed: 33353469
Front Physiol. 2021 Dec 14;12:771899
pubmed: 34970156
Cytokine. 2015 Mar;72(1):1-8
pubmed: 25514671
Psychosom Med. 2012 Jan;74(1):46-54
pubmed: 22210239
BMJ Open. 2014 Feb 07;4(2):e003973
pubmed: 24508851
Mol Neurobiol. 2019 Sep;56(9):6581-6585
pubmed: 30895436
Front Neurosci. 2021 Dec 15;15:748426
pubmed: 34975370
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):E134
pubmed: 20660311
PeerJ. 2018 Jan 22;6:e4282
pubmed: 29375937
Clin Exp Allergy. 2003 Oct;33(10):1450-6
pubmed: 14519154
Biomedicines. 2021 Nov 19;9(11):
pubmed: 34829952
Brain Behav Immun. 2020 Feb;84:106-114
pubmed: 31759091
J Transl Med. 2015 Sep 14;13:299
pubmed: 26370228
J Affect Disord. 2012 Dec 10;141(2-3):261-9
pubmed: 22572093
Clin Chim Acta. 2012 Oct 9;413(19-20):1525-31
pubmed: 22728138
Curr Opin HIV AIDS. 2010 Nov;5(6):463-6
pubmed: 20978388
Physiol Meas. 2012 Feb;33(2):231-41
pubmed: 22273713
Brain Connect. 2018 Feb;8(1):33-39
pubmed: 29152994
Front Immunol. 2018 May 09;9:1028
pubmed: 29867995
PLoS One. 2020 Jul 21;15(7):e0236148
pubmed: 32692761
J Transl Med. 2012 May 09;10:88
pubmed: 22571715
Biol Psychol. 2016 Jul;118:88-93
pubmed: 27224647
J Affect Disord. 2012 Feb;136(3):933-9
pubmed: 21975140
Mol Med. 2018 Aug 14;24(1):44
pubmed: 30134818
Gene Regul Syst Bio. 2016 Aug 28;10:85-93
pubmed: 27594784
Fatigue. 2020;8(4):226-244
pubmed: 33777500