Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Identifieur interne : 000137 ( Main/Exploration ); précédent : 000136; suivant : 000138Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Auteurs : Daniel Missailidis [Australie] ; Oana Sanislav [Australie] ; Claire Y. Allan [Australie] ; Sarah J. Annesley [Australie] ; Paul R. Fisher [Australie]Source :
- International journal of molecular sciences [ 1422-0067 ] ; 2020.
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood mononuclear cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase Target Of Rapamycin Complex 1 (TORC1). These differences were correlated with disease severity, as measured by the Richardson and Lidbury weighted standing test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here, we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and receiver operating characteristic (ROC) curve analysis. We found that results from three different tests-lymphocyte death rate, mitochondrial respiratory function and TORC1 activity-could each individually serve as a biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination, they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.
DOI: 10.3390/ijms21031142
PubMed: 32046336
PubMed Central: PMC7037777
Affiliations:
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Annesley</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086</wicri:regionArea><wicri:noRegion>VIC 3086</wicri:noRegion></affiliation></author><author><name sortKey="Fisher, Paul R" sort="Fisher, Paul R" uniqKey="Fisher P" first="Paul R" last="Fisher">Paul R. Fisher</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086</wicri:regionArea><wicri:noRegion>VIC 3086</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of molecular sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood mononuclear cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase Target Of Rapamycin Complex 1 (TORC1). These differences were correlated with disease severity, as measured by the Richardson and Lidbury weighted standing test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here, we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and receiver operating characteristic (ROC) curve analysis. We found that results from three different tests-lymphocyte death rate, mitochondrial respiratory function and TORC1 activity-could each individually serve as a biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination, they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32046336</PMID><DateRevised><Year>2020</Year><Month>03</Month><Day>13</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1422-0067</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><Issue>3</Issue><PubDate><Year>2020</Year><Month>Feb</Month><Day>08</Day></PubDate></JournalIssue><Title>International journal of molecular sciences</Title><ISOAbbreviation>Int J Mol Sci</ISOAbbreviation></Journal><ArticleTitle>Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">E1142</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms21031142</ELocationID><Abstract><AbstractText>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood mononuclear cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase Target Of Rapamycin Complex 1 (TORC1). These differences were correlated with disease severity, as measured by the Richardson and Lidbury weighted standing test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here, we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and receiver operating characteristic (ROC) curve analysis. We found that results from three different tests-lymphocyte death rate, mitochondrial respiratory function and TORC1 activity-could each individually serve as a biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination, they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Missailidis</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sanislav</LastName><ForeName>Oana</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allan</LastName><ForeName>Claire Y</ForeName><Initials>CY</Initials><AffiliationInfo><Affiliation>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Annesley</LastName><ForeName>Sarah J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fisher</LastName><ForeName>Paul R</ForeName><Initials>PR</Initials><AffiliationInfo><Affiliation>Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MAS2016F063 and MAS2018F00026</GrantID><Agency>Judith Jane Mason and Harold Stannett Williams Memorial Foundation</Agency><Country></Country></Grant><Grant><GrantID>NA</GrantID><Agency>McCusker Charitable Foundation</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">ME/CFS</Keyword><Keyword MajorTopicYN="N">Seahorse respirometry</Keyword><Keyword MajorTopicYN="N">TORC1</Keyword><Keyword MajorTopicYN="N">biomarker</Keyword><Keyword MajorTopicYN="N">chronic fatigue syndrome</Keyword><Keyword MajorTopicYN="N">complex V</Keyword><Keyword MajorTopicYN="N">diagnosis</Keyword><Keyword MajorTopicYN="N">mitochondria</Keyword><Keyword MajorTopicYN="N">myalgic encephalomyelitis</Keyword></KeywordList><CoiStatement>The authors declare no conflict of interest.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate 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sortKey="Missailidis, Daniel" sort="Missailidis, Daniel" uniqKey="Missailidis D" first="Daniel" last="Missailidis">Daniel Missailidis</name></noRegion><name sortKey="Allan, Claire Y" sort="Allan, Claire Y" uniqKey="Allan C" first="Claire Y" last="Allan">Claire Y. Allan</name><name sortKey="Annesley, Sarah J" sort="Annesley, Sarah J" uniqKey="Annesley S" first="Sarah J" last="Annesley">Sarah J. Annesley</name><name sortKey="Fisher, Paul R" sort="Fisher, Paul R" uniqKey="Fisher P" first="Paul R" last="Fisher">Paul R. Fisher</name><name sortKey="Sanislav, Oana" sort="Sanislav, Oana" uniqKey="Sanislav O" first="Oana" last="Sanislav">Oana Sanislav</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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