Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology
Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give...
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| creator | Michael, Benedict D Griffiths, Michael J Granerod, Julia Brown, David Davies, Nicholas W S Borrow, Ray Solomon, Tom |
| description | Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.
We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.
Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p |
| doi_str_mv | 10.1371/journal.pone.0146288 |
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We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.
Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).
Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0146288</identifier><identifier>PMID: 26808276</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Bacterial Infections - blood ; Bacterial Infections - cerebrospinal fluid ; Biology and Life Sciences ; Biomarkers ; Brain ; Cell Adhesion Molecules - blood ; Cell Adhesion Molecules - cerebrospinal fluid ; Cerebrospinal fluid ; Chemokines ; Chemokines - cerebrospinal fluid ; Chemokines - classification ; Classification ; Cytokines ; Cytokines - blood ; Cytokines - cerebrospinal fluid ; Diagnosis, Differential ; Diagnostic tests ; Disease ; Encephalitis ; Encephalitis - blood ; Encephalitis - cerebrospinal fluid ; Encephalitis - etiology ; Encephalitis - immunology ; Encephalitis, Viral - blood ; Encephalitis, Viral - cerebrospinal fluid ; Encephalitis, Viral - diagnosis ; England - epidemiology ; Etiology ; Female ; Herpes viruses ; Humans ; Infections ; Infectious diseases ; Infectious Encephalitis - blood ; Infectious Encephalitis - cerebrospinal fluid ; Infectious Encephalitis - diagnosis ; Inflammation ; Influenza ; Leukocyte Count ; Leukocytes (neutrophilic) ; Male ; Measurement methods ; Medicine and Health Sciences ; Multicenter Studies as Topic ; Multivariate analysis ; Mycoses - blood ; Mycoses - cerebrospinal fluid ; Mycoses - diagnosis ; Neutrophils ; Paraneoplastic Syndromes, Nervous System - blood ; Paraneoplastic Syndromes, Nervous System - cerebrospinal fluid ; Paraneoplastic Syndromes, Nervous System - diagnosis ; Pathogenesis ; Patients ; People and places ; Peroxidase ; Peroxidase - blood ; Peroxidase - cerebrospinal fluid ; Public health ; R&D ; Research & development ; Retrospective Studies ; Toxoplasmosis, Cerebral - blood ; Toxoplasmosis, Cerebral - cerebrospinal fluid ; Toxoplasmosis, Cerebral - diagnosis ; Zoonoses</subject><ispartof>PloS one, 2016-01, Vol.11 (1), p.e0146288-e0146288</ispartof><rights>2016 Michael et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Michael et al 2016 Michael et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-a11c373aad06158944c92060a4bd7bb0f90ad51da9f031377709925b7cb64b663</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726626/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726626/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26808276$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Proost, Paul</contributor><creatorcontrib>Michael, Benedict D</creatorcontrib><creatorcontrib>Griffiths, Michael J</creatorcontrib><creatorcontrib>Granerod, Julia</creatorcontrib><creatorcontrib>Brown, David</creatorcontrib><creatorcontrib>Davies, Nicholas W S</creatorcontrib><creatorcontrib>Borrow, Ray</creatorcontrib><creatorcontrib>Solomon, Tom</creatorcontrib><title>Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.
We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.
Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).
Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.</description><subject>Adult</subject><subject>Bacterial Infections - blood</subject><subject>Bacterial Infections - cerebrospinal fluid</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Brain</subject><subject>Cell Adhesion Molecules - blood</subject><subject>Cell Adhesion Molecules - cerebrospinal fluid</subject><subject>Cerebrospinal fluid</subject><subject>Chemokines</subject><subject>Chemokines - cerebrospinal fluid</subject><subject>Chemokines - classification</subject><subject>Classification</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Cytokines - cerebrospinal fluid</subject><subject>Diagnosis, Differential</subject><subject>Diagnostic tests</subject><subject>Disease</subject><subject>Encephalitis</subject><subject>Encephalitis - blood</subject><subject>Encephalitis - cerebrospinal fluid</subject><subject>Encephalitis - etiology</subject><subject>Encephalitis - immunology</subject><subject>Encephalitis, Viral - blood</subject><subject>Encephalitis, Viral - cerebrospinal fluid</subject><subject>Encephalitis, Viral - diagnosis</subject><subject>England - epidemiology</subject><subject>Etiology</subject><subject>Female</subject><subject>Herpes viruses</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Infectious Encephalitis - blood</subject><subject>Infectious Encephalitis - cerebrospinal fluid</subject><subject>Infectious Encephalitis - diagnosis</subject><subject>Inflammation</subject><subject>Influenza</subject><subject>Leukocyte Count</subject><subject>Leukocytes (neutrophilic)</subject><subject>Male</subject><subject>Measurement methods</subject><subject>Medicine and Health Sciences</subject><subject>Multicenter Studies as Topic</subject><subject>Multivariate analysis</subject><subject>Mycoses - blood</subject><subject>Mycoses - cerebrospinal fluid</subject><subject>Mycoses - diagnosis</subject><subject>Neutrophils</subject><subject>Paraneoplastic Syndromes, Nervous System - blood</subject><subject>Paraneoplastic Syndromes, Nervous System - cerebrospinal fluid</subject><subject>Paraneoplastic Syndromes, Nervous System - diagnosis</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>People and places</subject><subject>Peroxidase</subject><subject>Peroxidase - blood</subject><subject>Peroxidase - cerebrospinal fluid</subject><subject>Public health</subject><subject>R&D</subject><subject>Research & development</subject><subject>Retrospective Studies</subject><subject>Toxoplasmosis, Cerebral - blood</subject><subject>Toxoplasmosis, Cerebral - cerebrospinal fluid</subject><subject>Toxoplasmosis, Cerebral - diagnosis</subject><subject>Zoonoses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAUjBCIfsA_QBCJSw_N4m_Hl0pVVGClIjjQs-U4L7veJvZiJ6D992R306pFnGw_z8x7bzRZ9g6jBaYSf9qEMXrTLbbBwwJhJkhZvshOsaKkEATRl0_uJ9lZShuEOC2FeJ2dEFGikkhxmg3V2kRjB4guDc7m1W4I985DbnyTV2voj68fMbSug5Q7n994C9u16dzgUh7afOlbsIMLY7rMl30_eii-QePMAM3lQebO3_vwx-fXMKG6sNq9yV61pkvwdj7Ps7vPNz-rr8Xt9y_L6vq2sJyIoTAYWyqpMQ0SmJeKMasIEsiwupF1jVqFTMNxY1SL6OSJlEgpwmtpa8FqIeh59uGou-1C0rNhSWMpECKSMjkhlkdEE8xGb6PrTdzpYJw-FEJcaRMnXzrQVKhWSS4tA8lKqRQ3lBPJG6h5yct9t6u521j30FjwQzTdM9HnP96t9Sr81kwSIche4GIWiOHXCGnQvUsWus54mNw9zK0IkZJN0I__QP-_HTuibAwpRWgfh8FI70P0wNL7EOk5RBPt_dNFHkkPqaF_AVu0xTM</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Michael, Benedict D</creator><creator>Griffiths, Michael J</creator><creator>Granerod, Julia</creator><creator>Brown, David</creator><creator>Davies, Nicholas W S</creator><creator>Borrow, Ray</creator><creator>Solomon, Tom</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160101</creationdate><title>Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology</title><author>Michael, Benedict D ; Griffiths, Michael J ; Granerod, Julia ; Brown, David ; Davies, Nicholas W S ; Borrow, Ray ; Solomon, Tom</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-a11c373aad06158944c92060a4bd7bb0f90ad51da9f031377709925b7cb64b663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Bacterial Infections - blood</topic><topic>Bacterial Infections - cerebrospinal fluid</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Brain</topic><topic>Cell Adhesion Molecules - blood</topic><topic>Cell Adhesion Molecules - cerebrospinal fluid</topic><topic>Cerebrospinal fluid</topic><topic>Chemokines</topic><topic>Chemokines - cerebrospinal fluid</topic><topic>Chemokines - classification</topic><topic>Classification</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Cytokines - cerebrospinal fluid</topic><topic>Diagnosis, Differential</topic><topic>Diagnostic tests</topic><topic>Disease</topic><topic>Encephalitis</topic><topic>Encephalitis - blood</topic><topic>Encephalitis - cerebrospinal fluid</topic><topic>Encephalitis - etiology</topic><topic>Encephalitis - immunology</topic><topic>Encephalitis, Viral - blood</topic><topic>Encephalitis, Viral - cerebrospinal fluid</topic><topic>Encephalitis, Viral - diagnosis</topic><topic>England - epidemiology</topic><topic>Etiology</topic><topic>Female</topic><topic>Herpes viruses</topic><topic>Humans</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Infectious Encephalitis - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Michael, Benedict D</au><au>Griffiths, Michael J</au><au>Granerod, Julia</au><au>Brown, David</au><au>Davies, Nicholas W S</au><au>Borrow, Ray</au><au>Solomon, Tom</au><au>Proost, Paul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>11</volume><issue>1</issue><spage>e0146288</spage><epage>e0146288</epage><pages>e0146288-e0146288</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.
We measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.
Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).
Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26808276</pmid><doi>10.1371/journal.pone.0146288</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-01, Vol.11 (1), p.e0146288-e0146288 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1760027347 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Bacterial Infections - blood Bacterial Infections - cerebrospinal fluid Biology and Life Sciences Biomarkers Brain Cell Adhesion Molecules - blood Cell Adhesion Molecules - cerebrospinal fluid Cerebrospinal fluid Chemokines Chemokines - cerebrospinal fluid Chemokines - classification Classification Cytokines Cytokines - blood Cytokines - cerebrospinal fluid Diagnosis, Differential Diagnostic tests Disease Encephalitis Encephalitis - blood Encephalitis - cerebrospinal fluid Encephalitis - etiology Encephalitis - immunology Encephalitis, Viral - blood Encephalitis, Viral - cerebrospinal fluid Encephalitis, Viral - diagnosis England - epidemiology Etiology Female Herpes viruses Humans Infections Infectious diseases Infectious Encephalitis - blood Infectious Encephalitis - cerebrospinal fluid Infectious Encephalitis - diagnosis Inflammation Influenza Leukocyte Count Leukocytes (neutrophilic) Male Measurement methods Medicine and Health Sciences Multicenter Studies as Topic Multivariate analysis Mycoses - blood Mycoses - cerebrospinal fluid Mycoses - diagnosis Neutrophils Paraneoplastic Syndromes, Nervous System - blood Paraneoplastic Syndromes, Nervous System - cerebrospinal fluid Paraneoplastic Syndromes, Nervous System - diagnosis Pathogenesis Patients People and places Peroxidase Peroxidase - blood Peroxidase - cerebrospinal fluid Public health R&D Research & development Retrospective Studies Toxoplasmosis, Cerebral - blood Toxoplasmosis, Cerebral - cerebrospinal fluid Toxoplasmosis, Cerebral - diagnosis Zoonoses |
| title | Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology |
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