Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL‐22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status
Background: We analyzed the influence of Crohn's disease (CD)‐associated IL23R gene variants on IL‐22 that is expressed in IL‐23R+ Th17 cells. Methods: IL‐22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL‐6, TNF‐α, IL‐17A, IL‐17...
Gespeichert in:
| Veröffentlicht in: | Inflammatory bowel diseases 2008-02, Vol.14 (2), p.204-212 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 212 |
|---|---|
| container_issue | 2 |
| container_start_page | 204 |
| container_title | Inflammatory bowel diseases |
| container_volume | 14 |
| creator | Schmechel, Silke Konrad, Astrid Diegelmann, Julia Glas, Jürgen Wetzke, Martin Paschos, Ekaterini Lohse, Peter Göke, Burkhard Brand, Stephan |
| description | Background: We analyzed the influence of Crohn's disease (CD)‐associated IL23R gene variants on IL‐22 that is expressed in IL‐23R+ Th17 cells.
Methods: IL‐22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL‐6, TNF‐α, IL‐17A, IL‐17F, C‐reactive protein (CRP), and leukocyte count. In all patients, genotyping for 10 CD‐associated IL23R single nucleotide polymorphisms (SNPs) and the 3 main CD‐associated CARD15 variants was performed.
Results: There was a highly significant increase in IL‐22 serum expression in CD patients compared to healthy controls (P = 2.53 × 10−9). IL‐22 serum levels correlated with disease activity: IL‐22 levels in patients with a Crohn's disease activity index (CDAI) >150 were significantly higher than in patients with a CDAI |
| doi_str_mv | 10.1002/ibd.20315 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_902333783</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>902333783</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3905-8b2ba8219941b3ebd9005f30d9857815dba77c4c59afda7d2a6c63c22b2fb0983</originalsourceid><addsrcrecordid>eNp9kUtuFDEQhi1EREJgwQWQV0QsOvGje2yzg4GQkVpCQmHd8qM6Y-hxD7Y70ew4AifiMJwkbmYECwTyokqqz5-q9CP0jJJzSgi78MadM8Jp8wCd0IYvqlrW9cPSEyEropQ8Ro9T-lzQ8tQjdEwlYUwuxAn60frwxYcbfAMBsrc4TcnCNnvjB593OI94Gcd1OEvY-QQ6Ab7zeY2v11RgC8OA-ynY7MfwCq_an9--M4YTxGmDB7iFIWEdAftg4_zVle4vnQ4O2zFGGHQ-yH-Pivh23mJmVi3jH-c1x7zbAk5Z5yk9QUe9HhI8PdRT9Ony3fXyqmo_vF8tX7eV5Yo0lTTMaMmoUjU1HIxThDQ9J07JRkjaOKOFsLVtlO6dFo7phV1wy5hhvSFK8lN0tvdu4_h1gpS7jU_z-TrAOKVOEcY5F5IX8sV_SUGoooqLAr7cgzaOKUXou230Gx13HSXdHGtXYu1-xVrY5wfpZDbg_pCHHAtwsQfu_AC7f5u61Zu3e-U9UCqu_g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70191937</pqid></control><display><type>article</type><title>Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL‐22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Oxford University Press Journals All Titles (1996-Current)</source><creator>Schmechel, Silke ; Konrad, Astrid ; Diegelmann, Julia ; Glas, Jürgen ; Wetzke, Martin ; Paschos, Ekaterini ; Lohse, Peter ; Göke, Burkhard ; Brand, Stephan</creator><creatorcontrib>Schmechel, Silke ; Konrad, Astrid ; Diegelmann, Julia ; Glas, Jürgen ; Wetzke, Martin ; Paschos, Ekaterini ; Lohse, Peter ; Göke, Burkhard ; Brand, Stephan</creatorcontrib><description>Background: We analyzed the influence of Crohn's disease (CD)‐associated IL23R gene variants on IL‐22 that is expressed in IL‐23R+ Th17 cells.
Methods: IL‐22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL‐6, TNF‐α, IL‐17A, IL‐17F, C‐reactive protein (CRP), and leukocyte count. In all patients, genotyping for 10 CD‐associated IL23R single nucleotide polymorphisms (SNPs) and the 3 main CD‐associated CARD15 variants was performed.
Results: There was a highly significant increase in IL‐22 serum expression in CD patients compared to healthy controls (P = 2.53 × 10−9). IL‐22 serum levels correlated with disease activity: IL‐22 levels in patients with a Crohn's disease activity index (CDAI) >150 were significantly higher than in patients with a CDAI <150 (P = 0.001), while TNF‐α and IL‐6 were not significantly different between these 2 groups. Analyzing the effect of 10 IL23R variants on IL‐22 serum levels, we demonstrated that the quotients of mean IL‐22 serum levels of carriers of the minor allele to the mean serum IL‐22 in wildtype carriers correlated highly with the corresponding CD susceptibility risk for each gene variant (r = 0.807). The IL‐22 levels in carriers of CD risk‐increasing IL23R variants were significantly higher than in carriers of CD risk‐decreasing IL23R variants (P = 0.008).
Conclusions: The Th17 cytokine IL‐22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL‐6 and TNF‐α. IL23R genotypes influence IL‐22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.
(Inflamm Bowel Dis 2007)</description><identifier>ISSN: 1078-0998</identifier><identifier>EISSN: 1536-4844</identifier><identifier>DOI: 10.1002/ibd.20315</identifier><identifier>PMID: 18022867</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adolescent ; Adult ; Aged ; Biomarkers - blood ; CARD15 ; Case-Control Studies ; Crohn Disease - genetics ; Crohn Disease - immunology ; Crohn's disease ; Female ; Genetic Predisposition to Disease ; genetics ; Germany ; Humans ; IL‐17A ; IL‐17F ; IL‐22 ; IL‐23R ; IL‐6 ; inflammatory bowel disease ; Interleukin-22 ; Interleukins - blood ; Male ; Middle Aged ; NOD2 ; Nod2 Signaling Adaptor Protein - genetics ; polymorphism ; Polymorphism, Single Nucleotide ; Receptors, Interleukin - genetics ; Receptors, Interleukin - immunology ; T-Lymphocytes, Helper-Inducer - immunology ; Th17 cells ; TNF‐α ; ulcerative colitis ; White People - genetics</subject><ispartof>Inflammatory bowel diseases, 2008-02, Vol.14 (2), p.204-212</ispartof><rights>Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3905-8b2ba8219941b3ebd9005f30d9857815dba77c4c59afda7d2a6c63c22b2fb0983</citedby><cites>FETCH-LOGICAL-c3905-8b2ba8219941b3ebd9005f30d9857815dba77c4c59afda7d2a6c63c22b2fb0983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fibd.20315$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fibd.20315$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1413,27906,27907,45556,45557</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18022867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmechel, Silke</creatorcontrib><creatorcontrib>Konrad, Astrid</creatorcontrib><creatorcontrib>Diegelmann, Julia</creatorcontrib><creatorcontrib>Glas, Jürgen</creatorcontrib><creatorcontrib>Wetzke, Martin</creatorcontrib><creatorcontrib>Paschos, Ekaterini</creatorcontrib><creatorcontrib>Lohse, Peter</creatorcontrib><creatorcontrib>Göke, Burkhard</creatorcontrib><creatorcontrib>Brand, Stephan</creatorcontrib><title>Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL‐22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status</title><title>Inflammatory bowel diseases</title><addtitle>Inflamm Bowel Dis</addtitle><description>Background: We analyzed the influence of Crohn's disease (CD)‐associated IL23R gene variants on IL‐22 that is expressed in IL‐23R+ Th17 cells.
Methods: IL‐22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL‐6, TNF‐α, IL‐17A, IL‐17F, C‐reactive protein (CRP), and leukocyte count. In all patients, genotyping for 10 CD‐associated IL23R single nucleotide polymorphisms (SNPs) and the 3 main CD‐associated CARD15 variants was performed.
Results: There was a highly significant increase in IL‐22 serum expression in CD patients compared to healthy controls (P = 2.53 × 10−9). IL‐22 serum levels correlated with disease activity: IL‐22 levels in patients with a Crohn's disease activity index (CDAI) >150 were significantly higher than in patients with a CDAI <150 (P = 0.001), while TNF‐α and IL‐6 were not significantly different between these 2 groups. Analyzing the effect of 10 IL23R variants on IL‐22 serum levels, we demonstrated that the quotients of mean IL‐22 serum levels of carriers of the minor allele to the mean serum IL‐22 in wildtype carriers correlated highly with the corresponding CD susceptibility risk for each gene variant (r = 0.807). The IL‐22 levels in carriers of CD risk‐increasing IL23R variants were significantly higher than in carriers of CD risk‐decreasing IL23R variants (P = 0.008).
Conclusions: The Th17 cytokine IL‐22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL‐6 and TNF‐α. IL23R genotypes influence IL‐22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.
(Inflamm Bowel Dis 2007)</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biomarkers - blood</subject><subject>CARD15</subject><subject>Case-Control Studies</subject><subject>Crohn Disease - genetics</subject><subject>Crohn Disease - immunology</subject><subject>Crohn's disease</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>genetics</subject><subject>Germany</subject><subject>Humans</subject><subject>IL‐17A</subject><subject>IL‐17F</subject><subject>IL‐22</subject><subject>IL‐23R</subject><subject>IL‐6</subject><subject>inflammatory bowel disease</subject><subject>Interleukin-22</subject><subject>Interleukins - blood</subject><subject>Male</subject><subject>Middle Aged</subject><subject>NOD2</subject><subject>Nod2 Signaling Adaptor Protein - genetics</subject><subject>polymorphism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptors, Interleukin - genetics</subject><subject>Receptors, Interleukin - immunology</subject><subject>T-Lymphocytes, Helper-Inducer - immunology</subject><subject>Th17 cells</subject><subject>TNF‐α</subject><subject>ulcerative colitis</subject><subject>White People - genetics</subject><issn>1078-0998</issn><issn>1536-4844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtuFDEQhi1EREJgwQWQV0QsOvGje2yzg4GQkVpCQmHd8qM6Y-hxD7Y70ew4AifiMJwkbmYECwTyokqqz5-q9CP0jJJzSgi78MadM8Jp8wCd0IYvqlrW9cPSEyEropQ8Ro9T-lzQ8tQjdEwlYUwuxAn60frwxYcbfAMBsrc4TcnCNnvjB593OI94Gcd1OEvY-QQ6Ab7zeY2v11RgC8OA-ynY7MfwCq_an9--M4YTxGmDB7iFIWEdAftg4_zVle4vnQ4O2zFGGHQ-yH-Pivh23mJmVi3jH-c1x7zbAk5Z5yk9QUe9HhI8PdRT9Ony3fXyqmo_vF8tX7eV5Yo0lTTMaMmoUjU1HIxThDQ9J07JRkjaOKOFsLVtlO6dFo7phV1wy5hhvSFK8lN0tvdu4_h1gpS7jU_z-TrAOKVOEcY5F5IX8sV_SUGoooqLAr7cgzaOKUXou230Gx13HSXdHGtXYu1-xVrY5wfpZDbg_pCHHAtwsQfu_AC7f5u61Zu3e-U9UCqu_g</recordid><startdate>200802</startdate><enddate>200802</enddate><creator>Schmechel, Silke</creator><creator>Konrad, Astrid</creator><creator>Diegelmann, Julia</creator><creator>Glas, Jürgen</creator><creator>Wetzke, Martin</creator><creator>Paschos, Ekaterini</creator><creator>Lohse, Peter</creator><creator>Göke, Burkhard</creator><creator>Brand, Stephan</creator><general>Wiley Subscription Services, Inc., A Wiley Company</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>7X8</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>200802</creationdate><title>Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL‐22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status</title><author>Schmechel, Silke ; Konrad, Astrid ; Diegelmann, Julia ; Glas, Jürgen ; Wetzke, Martin ; Paschos, Ekaterini ; Lohse, Peter ; Göke, Burkhard ; Brand, Stephan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3905-8b2ba8219941b3ebd9005f30d9857815dba77c4c59afda7d2a6c63c22b2fb0983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biomarkers - blood</topic><topic>CARD15</topic><topic>Case-Control Studies</topic><topic>Crohn Disease - genetics</topic><topic>Crohn Disease - immunology</topic><topic>Crohn's disease</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>genetics</topic><topic>Germany</topic><topic>Humans</topic><topic>IL‐17A</topic><topic>IL‐17F</topic><topic>IL‐22</topic><topic>IL‐23R</topic><topic>IL‐6</topic><topic>inflammatory bowel disease</topic><topic>Interleukin-22</topic><topic>Interleukins - blood</topic><topic>Male</topic><topic>Middle Aged</topic><topic>NOD2</topic><topic>Nod2 Signaling Adaptor Protein - genetics</topic><topic>polymorphism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptors, Interleukin - genetics</topic><topic>Receptors, Interleukin - immunology</topic><topic>T-Lymphocytes, Helper-Inducer - immunology</topic><topic>Th17 cells</topic><topic>TNF‐α</topic><topic>ulcerative colitis</topic><topic>White People - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmechel, Silke</creatorcontrib><creatorcontrib>Konrad, Astrid</creatorcontrib><creatorcontrib>Diegelmann, Julia</creatorcontrib><creatorcontrib>Glas, Jürgen</creatorcontrib><creatorcontrib>Wetzke, Martin</creatorcontrib><creatorcontrib>Paschos, Ekaterini</creatorcontrib><creatorcontrib>Lohse, Peter</creatorcontrib><creatorcontrib>Göke, Burkhard</creatorcontrib><creatorcontrib>Brand, Stephan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Inflammatory bowel diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmechel, Silke</au><au>Konrad, Astrid</au><au>Diegelmann, Julia</au><au>Glas, Jürgen</au><au>Wetzke, Martin</au><au>Paschos, Ekaterini</au><au>Lohse, Peter</au><au>Göke, Burkhard</au><au>Brand, Stephan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL‐22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status</atitle><jtitle>Inflammatory bowel diseases</jtitle><addtitle>Inflamm Bowel Dis</addtitle><date>2008-02</date><risdate>2008</risdate><volume>14</volume><issue>2</issue><spage>204</spage><epage>212</epage><pages>204-212</pages><issn>1078-0998</issn><eissn>1536-4844</eissn><abstract>Background: We analyzed the influence of Crohn's disease (CD)‐associated IL23R gene variants on IL‐22 that is expressed in IL‐23R+ Th17 cells.
Methods: IL‐22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL‐6, TNF‐α, IL‐17A, IL‐17F, C‐reactive protein (CRP), and leukocyte count. In all patients, genotyping for 10 CD‐associated IL23R single nucleotide polymorphisms (SNPs) and the 3 main CD‐associated CARD15 variants was performed.
Results: There was a highly significant increase in IL‐22 serum expression in CD patients compared to healthy controls (P = 2.53 × 10−9). IL‐22 serum levels correlated with disease activity: IL‐22 levels in patients with a Crohn's disease activity index (CDAI) >150 were significantly higher than in patients with a CDAI <150 (P = 0.001), while TNF‐α and IL‐6 were not significantly different between these 2 groups. Analyzing the effect of 10 IL23R variants on IL‐22 serum levels, we demonstrated that the quotients of mean IL‐22 serum levels of carriers of the minor allele to the mean serum IL‐22 in wildtype carriers correlated highly with the corresponding CD susceptibility risk for each gene variant (r = 0.807). The IL‐22 levels in carriers of CD risk‐increasing IL23R variants were significantly higher than in carriers of CD risk‐decreasing IL23R variants (P = 0.008).
Conclusions: The Th17 cytokine IL‐22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL‐6 and TNF‐α. IL23R genotypes influence IL‐22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.
(Inflamm Bowel Dis 2007)</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>18022867</pmid><doi>10.1002/ibd.20315</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0998 |
| ispartof | Inflammatory bowel diseases, 2008-02, Vol.14 (2), p.204-212 |
| issn | 1078-0998 1536-4844 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_902333783 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Adolescent Adult Aged Biomarkers - blood CARD15 Case-Control Studies Crohn Disease - genetics Crohn Disease - immunology Crohn's disease Female Genetic Predisposition to Disease genetics Germany Humans IL‐17A IL‐17F IL‐22 IL‐23R IL‐6 inflammatory bowel disease Interleukin-22 Interleukins - blood Male Middle Aged NOD2 Nod2 Signaling Adaptor Protein - genetics polymorphism Polymorphism, Single Nucleotide Receptors, Interleukin - genetics Receptors, Interleukin - immunology T-Lymphocytes, Helper-Inducer - immunology Th17 cells TNF‐α ulcerative colitis White People - genetics |
| title | Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL‐22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T10%3A13%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Linking%20genetic%20susceptibility%20to%20Crohn's%20disease%20with%20Th17%20cell%20function:%20IL%E2%80%9022%20serum%20levels%20are%20increased%20in%20Crohn's%20disease%20and%20correlate%20with%20disease%20activity%20and%20IL23R%20genotype%20status&rft.jtitle=Inflammatory%20bowel%20diseases&rft.au=Schmechel,%20Silke&rft.date=2008-02&rft.volume=14&rft.issue=2&rft.spage=204&rft.epage=212&rft.pages=204-212&rft.issn=1078-0998&rft.eissn=1536-4844&rft_id=info:doi/10.1002/ibd.20315&rft_dat=%3Cproquest_cross%3E902333783%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70191937&rft_id=info:pmid/18022867&rfr_iscdi=true |