Elevated Levels of IL-23 in a Subset of Patients With Post–Lyme Disease Symptoms Following Erythema Migrans
Background. The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms. Methods. The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 an...
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description | Background. The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms. Methods. The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 antibiotic-treated European patients with erythema migrans, 45 with post-Lyme symptoms and 41 without symptoms, who were evaluated prior to treatment and 2, 6, and 12 months thereafter. Results. At study entry, significant differences between groups were observed for the type 1 helper T cell (T H 1)–associated chemokines CXCL9 and CXCL10, which were associated with negative Borrelia cultures, and the type 17 helper T cell (T H 17)–associated cytokine interleukin 23 (IL-23), which was associated with positive cultures and the development of post-Lyme symptoms (P ≤ .02). Moreover, of the 41 patients with detectable IL-23 levels, 25 (61%) developed post-Lyme symptoms, and all 7 with IL-23 levels ≥230 ng/mL had such symptoms. Furthermore, antibody responses to the ECGF autoantigen were more common in patients with post-Lyme symptoms (P = .07) and were correlated directly with IL-23 levels (P = .02). Despite the presence of post-Lyme symptoms, all posttreatment culture results were negative, antiborrelial antibody responses declined, and there were no objective signs of disseminated disease, suggesting that spirochetal eradication had occurred with treatment in all patients. Conclusions. High T H 1-associated responses correlated with more effective immune-mediated spirochetal killing, whereas high T H 17-associated immune responses, often accompanied by autoantibodies, correlated with post-Lyme symptoms, providing a new paradigm for the study of postinfectious symptoms in a subset of patients with Lyme disease. |
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The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms. Methods. The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 antibiotic-treated European patients with erythema migrans, 45 with post-Lyme symptoms and 41 without symptoms, who were evaluated prior to treatment and 2, 6, and 12 months thereafter. Results. At study entry, significant differences between groups were observed for the type 1 helper T cell (T H 1)–associated chemokines CXCL9 and CXCL10, which were associated with negative Borrelia cultures, and the type 17 helper T cell (T H 17)–associated cytokine interleukin 23 (IL-23), which was associated with positive cultures and the development of post-Lyme symptoms (P ≤ .02). Moreover, of the 41 patients with detectable IL-23 levels, 25 (61%) developed post-Lyme symptoms, and all 7 with IL-23 levels ≥230 ng/mL had such symptoms. Furthermore, antibody responses to the ECGF autoantigen were more common in patients with post-Lyme symptoms (P = .07) and were correlated directly with IL-23 levels (P = .02). Despite the presence of post-Lyme symptoms, all posttreatment culture results were negative, antiborrelial antibody responses declined, and there were no objective signs of disseminated disease, suggesting that spirochetal eradication had occurred with treatment in all patients. Conclusions. High T H 1-associated responses correlated with more effective immune-mediated spirochetal killing, whereas high T H 17-associated immune responses, often accompanied by autoantibodies, correlated with post-Lyme symptoms, providing a new paradigm for the study of postinfectious symptoms in a subset of patients with Lyme disease.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/cit735</identifier><identifier>PMID: 24218102</identifier><identifier>CODEN: CIDIEL</identifier><language>eng</language><publisher>Oxford: OXFORD UNIVERSITY PRESS</publisher><subject>Adolescent ; Adult ; Aged ; and Commentaries ; Antibiotics ; Antibodies ; ARTICLES AND COMMENTARIES ; Autoantibodies - blood ; Bacterial diseases ; Biological and medical sciences ; Borrelia ; Borrelia infections ; Chemokines ; Correlation analysis ; Cytokines ; Erythema ; Erythema Chronicum Migrans - immunology ; Erythema multiforme ; Europe ; Female ; Human bacterial diseases ; Humans ; Infections ; Infectious diseases ; Interleukin-23 - blood ; Lyme disease ; Male ; Medical sciences ; Medical treatment ; Middle Aged ; Symptomatology ; T cell receptors ; Th1 Cells - immunology ; Th17 Cells - immunology ; Thymidine Phosphorylase - immunology ; Tropical bacterial diseases ; Young Adult</subject><ispartof>Clinical infectious diseases, 2014-02, Vol.58 (3), p.372-380</ispartof><rights>Copyright © 2014 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com . 2013</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Oxford University Press, UK Feb 1, 2014</rights><rights>The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: . 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-53e5cec5c57e43b08ee80dfaafdb48f9c1f0fc64e2c6d03e317fcbd7a3cc71383</citedby><cites>FETCH-LOGICAL-c488t-53e5cec5c57e43b08ee80dfaafdb48f9c1f0fc64e2c6d03e317fcbd7a3cc71383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24031229$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24031229$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,1584,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28319462$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24218102$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strle, Klemen</creatorcontrib><creatorcontrib>Stupica, Daša</creatorcontrib><creatorcontrib>Drouin, Elise E.</creatorcontrib><creatorcontrib>Steere, Allen C.</creatorcontrib><creatorcontrib>Strle, Franc</creatorcontrib><title>Elevated Levels of IL-23 in a Subset of Patients With Post–Lyme Disease Symptoms Following Erythema Migrans</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Background. The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms. Methods. The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 antibiotic-treated European patients with erythema migrans, 45 with post-Lyme symptoms and 41 without symptoms, who were evaluated prior to treatment and 2, 6, and 12 months thereafter. Results. At study entry, significant differences between groups were observed for the type 1 helper T cell (T H 1)–associated chemokines CXCL9 and CXCL10, which were associated with negative Borrelia cultures, and the type 17 helper T cell (T H 17)–associated cytokine interleukin 23 (IL-23), which was associated with positive cultures and the development of post-Lyme symptoms (P ≤ .02). Moreover, of the 41 patients with detectable IL-23 levels, 25 (61%) developed post-Lyme symptoms, and all 7 with IL-23 levels ≥230 ng/mL had such symptoms. Furthermore, antibody responses to the ECGF autoantigen were more common in patients with post-Lyme symptoms (P = .07) and were correlated directly with IL-23 levels (P = .02). Despite the presence of post-Lyme symptoms, all posttreatment culture results were negative, antiborrelial antibody responses declined, and there were no objective signs of disseminated disease, suggesting that spirochetal eradication had occurred with treatment in all patients. Conclusions. High T H 1-associated responses correlated with more effective immune-mediated spirochetal killing, whereas high T H 17-associated immune responses, often accompanied by autoantibodies, correlated with post-Lyme symptoms, providing a new paradigm for the study of postinfectious symptoms in a subset of patients with Lyme disease.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>and Commentaries</subject><subject>Antibiotics</subject><subject>Antibodies</subject><subject>ARTICLES AND COMMENTARIES</subject><subject>Autoantibodies - blood</subject><subject>Bacterial diseases</subject><subject>Biological and medical sciences</subject><subject>Borrelia</subject><subject>Borrelia infections</subject><subject>Chemokines</subject><subject>Correlation analysis</subject><subject>Cytokines</subject><subject>Erythema</subject><subject>Erythema Chronicum Migrans - immunology</subject><subject>Erythema multiforme</subject><subject>Europe</subject><subject>Female</subject><subject>Human bacterial diseases</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Interleukin-23 - blood</subject><subject>Lyme disease</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medical treatment</subject><subject>Middle Aged</subject><subject>Symptomatology</subject><subject>T cell receptors</subject><subject>Th1 Cells - immunology</subject><subject>Th17 Cells - immunology</subject><subject>Thymidine Phosphorylase - immunology</subject><subject>Tropical bacterial diseases</subject><subject>Young Adult</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGKFDEQhhtR3HX14l0JiCBCa9JJppOLIOusLrS4sIrHkE5XZjJ0d8YkPTI338E39EnMOOM6evAQKqQ-_vpTf1E8JPgFwZK-NK7LJ9WU3ypOCad1OeOS3M53zEXJBBUnxb0YVxgTIjC_W5xUrCKC4Oq0GOY9bHSCDjWwgT4ib9FlU1YUuRFpdD21EdLu8UonB2OK6LNLS3TlY_rx7XuzHQC9cRF0BHS9HdbJDxFd-L73X924QPOwTUsYNHrvFkGP8X5xx-o-woNDPSs-Xcw_nr8rmw9vL89fN6VhQqSSU-AGDDe8BkZbLAAE7qzWtmuZsNIQi62ZMajMrMMUKKmtabtaU2NqQgU9K17tdddTO0BnsvGge7UObtBhq7x26u_O6JZq4TeKCokpw1ng2UEg-C8TxKQGFw30vR7BT1ERJvFM5hXyjD75B135KYz5e78oKWnNdtTzPWWCjzGAvTFDsNqlqHKKap9ihh8f279Bf8eWgacHQEeje5t3a1z8wwlKJJsdcX5a_3_goz23ismHo3mYkqqS9CfIBb5I</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>Strle, Klemen</creator><creator>Stupica, Daša</creator><creator>Drouin, Elise E.</creator><creator>Steere, Allen C.</creator><creator>Strle, Franc</creator><general>OXFORD UNIVERSITY PRESS</general><general>Oxford University Press</general><scope>IQODW</scope><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>7QL</scope><scope>7T2</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140201</creationdate><title>Elevated Levels of IL-23 in a Subset of Patients With Post–Lyme Disease Symptoms Following Erythema Migrans</title><author>Strle, Klemen ; Stupica, Daša ; Drouin, Elise E. ; Steere, Allen C. ; Strle, Franc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-53e5cec5c57e43b08ee80dfaafdb48f9c1f0fc64e2c6d03e317fcbd7a3cc71383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>and Commentaries</topic><topic>Antibiotics</topic><topic>Antibodies</topic><topic>ARTICLES AND COMMENTARIES</topic><topic>Autoantibodies - blood</topic><topic>Bacterial diseases</topic><topic>Biological and medical sciences</topic><topic>Borrelia</topic><topic>Borrelia infections</topic><topic>Chemokines</topic><topic>Correlation analysis</topic><topic>Cytokines</topic><topic>Erythema</topic><topic>Erythema Chronicum Migrans - immunology</topic><topic>Erythema multiforme</topic><topic>Europe</topic><topic>Female</topic><topic>Human bacterial diseases</topic><topic>Humans</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Interleukin-23 - blood</topic><topic>Lyme disease</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medical treatment</topic><topic>Middle Aged</topic><topic>Symptomatology</topic><topic>T cell receptors</topic><topic>Th1 Cells - immunology</topic><topic>Th17 Cells - immunology</topic><topic>Thymidine Phosphorylase - immunology</topic><topic>Tropical bacterial diseases</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strle, Klemen</creatorcontrib><creatorcontrib>Stupica, Daša</creatorcontrib><creatorcontrib>Drouin, Elise E.</creatorcontrib><creatorcontrib>Steere, Allen C.</creatorcontrib><creatorcontrib>Strle, Franc</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strle, Klemen</au><au>Stupica, Daša</au><au>Drouin, Elise E.</au><au>Steere, Allen C.</au><au>Strle, Franc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated Levels of IL-23 in a Subset of Patients With Post–Lyme Disease Symptoms Following Erythema Migrans</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>58</volume><issue>3</issue><spage>372</spage><epage>380</epage><pages>372-380</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><coden>CIDIEL</coden><abstract>Background. The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms. Methods. The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 antibiotic-treated European patients with erythema migrans, 45 with post-Lyme symptoms and 41 without symptoms, who were evaluated prior to treatment and 2, 6, and 12 months thereafter. Results. At study entry, significant differences between groups were observed for the type 1 helper T cell (T H 1)–associated chemokines CXCL9 and CXCL10, which were associated with negative Borrelia cultures, and the type 17 helper T cell (T H 17)–associated cytokine interleukin 23 (IL-23), which was associated with positive cultures and the development of post-Lyme symptoms (P ≤ .02). Moreover, of the 41 patients with detectable IL-23 levels, 25 (61%) developed post-Lyme symptoms, and all 7 with IL-23 levels ≥230 ng/mL had such symptoms. Furthermore, antibody responses to the ECGF autoantigen were more common in patients with post-Lyme symptoms (P = .07) and were correlated directly with IL-23 levels (P = .02). Despite the presence of post-Lyme symptoms, all posttreatment culture results were negative, antiborrelial antibody responses declined, and there were no objective signs of disseminated disease, suggesting that spirochetal eradication had occurred with treatment in all patients. Conclusions. High T H 1-associated responses correlated with more effective immune-mediated spirochetal killing, whereas high T H 17-associated immune responses, often accompanied by autoantibodies, correlated with post-Lyme symptoms, providing a new paradigm for the study of postinfectious symptoms in a subset of patients with Lyme disease.</abstract><cop>Oxford</cop><pub>OXFORD UNIVERSITY PRESS</pub><pmid>24218102</pmid><doi>10.1093/cid/cit735</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Aged and Commentaries Antibiotics Antibodies ARTICLES AND COMMENTARIES Autoantibodies - blood Bacterial diseases Biological and medical sciences Borrelia Borrelia infections Chemokines Correlation analysis Cytokines Erythema Erythema Chronicum Migrans - immunology Erythema multiforme Europe Female Human bacterial diseases Humans Infections Infectious diseases Interleukin-23 - blood Lyme disease Male Medical sciences Medical treatment Middle Aged Symptomatology T cell receptors Th1 Cells - immunology Th17 Cells - immunology Thymidine Phosphorylase - immunology Tropical bacterial diseases Young Adult |
title | Elevated Levels of IL-23 in a Subset of Patients With Post–Lyme Disease Symptoms Following Erythema Migrans |
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