Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency
No genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the “inducible costimulator” on activated T cells, due to a...
Gespeichert in:
| Veröffentlicht in: | Nature immunology 2003-03, Vol.4 (3), p.261-268 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 268 |
|---|---|
| container_issue | 3 |
| container_start_page | 261 |
| container_title | Nature immunology |
| container_volume | 4 |
| creator | Grimbacher, Bodo Hutloff, Andreas Schlesier, Michael Glocker, Erik Warnatz, Klaus Dräger, Ruth Eibel, Hermann Fischer, Beate Schäffer, Alejandro A. Mages, Hans W. Kroczek, Richard A. Peter, Hans H. |
| description | No genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the “inducible costimulator” on activated T cells, due to an inherited homozygous deletion in the ICOS gene. T cells from these individuals were normal with regard to subset distribution, activation, cytokine production and proliferation. In contrast, naive, switched and memory B cells were reduced. The phenotype of human ICOS deficiency, which differs in key aspects from that of the ICOS
−/−
mouse, suggests a critical involvement of ICOS in T cell help for late B cell differentiation, class-switching and memory B cell generation. |
| doi_str_mv | 10.1038/ni902 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_73060723</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A188808291</galeid><sourcerecordid>A188808291</sourcerecordid><originalsourceid>FETCH-LOGICAL-c489t-e473ccaf29231445ece964717b0355407639e9b63f95434eb3be6663d7e8c6e23</originalsourceid><addsrcrecordid>eNqFkl9rFDEUxYNYbK39ChIUBR-m5t8kM49l0XahULCKjyGTubOmTJI6yVTXT9-0u7hsESQPCTe_e-DcexA6oeSUEt58DK4l7Bk6ojVrK9ZS-fzvmzSH6GVKN4RQoaR4gQ4pq5UitTxC3y-ij3_WqzgnPMaUcBzwcnF1jV3CJqVoncnQ418u_8Cmn8dcxZAgYxu9jwHfmcmZbgTsvJ9D7GFw1kGw61foYDBjgpPtfYy-ff70dXFRXV6dLxdnl5UVTZsrEIpbawbWMk6FqMFCK4WiqiO8rgVRkrfQdpIPbS24gI53IKXkvYLGSmD8GL3f6N5O8ecMKWvvkoVxNAGKJ604kUQx_l-QNg2RgpECvnkC3sR5CsWEZoypmotHtbcbaGVG0C4MMU_GPijqs6LUkKasoFCn_6DK6cE7G0OZVqnvNXzYayhMht95ZeaU9PL6yz77bsPaqextgkHfTs6baa0p0Q-R0I-RKNzrrZ-589DvqG0GdpNJ5SusYNoZ3le6B39Wueg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>222753423</pqid></control><display><type>article</type><title>Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency</title><source>MEDLINE</source><source>Nature Journals Online</source><source>SpringerLink Journals - AutoHoldings</source><creator>Grimbacher, Bodo ; Hutloff, Andreas ; Schlesier, Michael ; Glocker, Erik ; Warnatz, Klaus ; Dräger, Ruth ; Eibel, Hermann ; Fischer, Beate ; Schäffer, Alejandro A. ; Mages, Hans W. ; Kroczek, Richard A. ; Peter, Hans H.</creator><creatorcontrib>Grimbacher, Bodo ; Hutloff, Andreas ; Schlesier, Michael ; Glocker, Erik ; Warnatz, Klaus ; Dräger, Ruth ; Eibel, Hermann ; Fischer, Beate ; Schäffer, Alejandro A. ; Mages, Hans W. ; Kroczek, Richard A. ; Peter, Hans H.</creatorcontrib><description>No genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the “inducible costimulator” on activated T cells, due to an inherited homozygous deletion in the ICOS gene. T cells from these individuals were normal with regard to subset distribution, activation, cytokine production and proliferation. In contrast, naive, switched and memory B cells were reduced. The phenotype of human ICOS deficiency, which differs in key aspects from that of the ICOS
−/−
mouse, suggests a critical involvement of ICOS in T cell help for late B cell differentiation, class-switching and memory B cell generation.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni902</identifier><identifier>PMID: 12577056</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Antigens, Differentiation, T-Lymphocyte - genetics ; B-Lymphocytes - physiology ; Biomedical and Life Sciences ; Biomedicine ; CD28 Antigens - immunology ; Cell differentiation ; Cell Differentiation - immunology ; Common Variable Immunodeficiency - genetics ; Homozygote ; Humans ; Immunoglobulin A - blood ; Immunoglobulin G - blood ; Immunoglobulin M - blood ; Immunologic Memory - immunology ; Immunology ; Inducible T-Cell Co-Stimulator Protein ; Infectious Diseases ; Receptors, Antigen, T-Cell - immunology ; Sequence Deletion ; T-Lymphocytes - physiology</subject><ispartof>Nature immunology, 2003-03, Vol.4 (3), p.261-268</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-e473ccaf29231445ece964717b0355407639e9b63f95434eb3be6663d7e8c6e23</citedby><cites>FETCH-LOGICAL-c489t-e473ccaf29231445ece964717b0355407639e9b63f95434eb3be6663d7e8c6e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ni902$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ni902$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12577056$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Grimbacher, Bodo</creatorcontrib><creatorcontrib>Hutloff, Andreas</creatorcontrib><creatorcontrib>Schlesier, Michael</creatorcontrib><creatorcontrib>Glocker, Erik</creatorcontrib><creatorcontrib>Warnatz, Klaus</creatorcontrib><creatorcontrib>Dräger, Ruth</creatorcontrib><creatorcontrib>Eibel, Hermann</creatorcontrib><creatorcontrib>Fischer, Beate</creatorcontrib><creatorcontrib>Schäffer, Alejandro A.</creatorcontrib><creatorcontrib>Mages, Hans W.</creatorcontrib><creatorcontrib>Kroczek, Richard A.</creatorcontrib><creatorcontrib>Peter, Hans H.</creatorcontrib><title>Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>No genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the “inducible costimulator” on activated T cells, due to an inherited homozygous deletion in the ICOS gene. T cells from these individuals were normal with regard to subset distribution, activation, cytokine production and proliferation. In contrast, naive, switched and memory B cells were reduced. The phenotype of human ICOS deficiency, which differs in key aspects from that of the ICOS
−/−
mouse, suggests a critical involvement of ICOS in T cell help for late B cell differentiation, class-switching and memory B cell generation.</description><subject>Antigens, Differentiation, T-Lymphocyte - genetics</subject><subject>B-Lymphocytes - physiology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CD28 Antigens - immunology</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - immunology</subject><subject>Common Variable Immunodeficiency - genetics</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Immunoglobulin A - blood</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin M - blood</subject><subject>Immunologic Memory - immunology</subject><subject>Immunology</subject><subject>Inducible T-Cell Co-Stimulator Protein</subject><subject>Infectious Diseases</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>Sequence Deletion</subject><subject>T-Lymphocytes - physiology</subject><issn>1529-2908</issn><issn>1529-2916</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</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><recordid>eNqFkl9rFDEUxYNYbK39ChIUBR-m5t8kM49l0XahULCKjyGTubOmTJI6yVTXT9-0u7hsESQPCTe_e-DcexA6oeSUEt58DK4l7Bk6ojVrK9ZS-fzvmzSH6GVKN4RQoaR4gQ4pq5UitTxC3y-ij3_WqzgnPMaUcBzwcnF1jV3CJqVoncnQ418u_8Cmn8dcxZAgYxu9jwHfmcmZbgTsvJ9D7GFw1kGw61foYDBjgpPtfYy-ff70dXFRXV6dLxdnl5UVTZsrEIpbawbWMk6FqMFCK4WiqiO8rgVRkrfQdpIPbS24gI53IKXkvYLGSmD8GL3f6N5O8ecMKWvvkoVxNAGKJ604kUQx_l-QNg2RgpECvnkC3sR5CsWEZoypmotHtbcbaGVG0C4MMU_GPijqs6LUkKasoFCn_6DK6cE7G0OZVqnvNXzYayhMht95ZeaU9PL6yz77bsPaqextgkHfTs6baa0p0Q-R0I-RKNzrrZ-589DvqG0GdpNJ5SusYNoZ3le6B39Wueg</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>Grimbacher, Bodo</creator><creator>Hutloff, Andreas</creator><creator>Schlesier, Michael</creator><creator>Glocker, Erik</creator><creator>Warnatz, Klaus</creator><creator>Dräger, Ruth</creator><creator>Eibel, Hermann</creator><creator>Fischer, Beate</creator><creator>Schäffer, Alejandro A.</creator><creator>Mages, Hans W.</creator><creator>Kroczek, Richard A.</creator><creator>Peter, Hans H.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</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>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20030301</creationdate><title>Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency</title><author>Grimbacher, Bodo ; Hutloff, Andreas ; Schlesier, Michael ; Glocker, Erik ; Warnatz, Klaus ; Dräger, Ruth ; Eibel, Hermann ; Fischer, Beate ; Schäffer, Alejandro A. ; Mages, Hans W. ; Kroczek, Richard A. ; Peter, Hans H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-e473ccaf29231445ece964717b0355407639e9b63f95434eb3be6663d7e8c6e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Antigens, Differentiation, T-Lymphocyte - genetics</topic><topic>B-Lymphocytes - physiology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CD28 Antigens - immunology</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - immunology</topic><topic>Common Variable Immunodeficiency - genetics</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Immunoglobulin A - blood</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin M - blood</topic><topic>Immunologic Memory - immunology</topic><topic>Immunology</topic><topic>Inducible T-Cell Co-Stimulator Protein</topic><topic>Infectious Diseases</topic><topic>Receptors, Antigen, T-Cell - immunology</topic><topic>Sequence Deletion</topic><topic>T-Lymphocytes - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grimbacher, Bodo</creatorcontrib><creatorcontrib>Hutloff, Andreas</creatorcontrib><creatorcontrib>Schlesier, Michael</creatorcontrib><creatorcontrib>Glocker, Erik</creatorcontrib><creatorcontrib>Warnatz, Klaus</creatorcontrib><creatorcontrib>Dräger, Ruth</creatorcontrib><creatorcontrib>Eibel, Hermann</creatorcontrib><creatorcontrib>Fischer, Beate</creatorcontrib><creatorcontrib>Schäffer, Alejandro A.</creatorcontrib><creatorcontrib>Mages, Hans W.</creatorcontrib><creatorcontrib>Kroczek, Richard A.</creatorcontrib><creatorcontrib>Peter, Hans H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grimbacher, Bodo</au><au>Hutloff, Andreas</au><au>Schlesier, Michael</au><au>Glocker, Erik</au><au>Warnatz, Klaus</au><au>Dräger, Ruth</au><au>Eibel, Hermann</au><au>Fischer, Beate</au><au>Schäffer, Alejandro A.</au><au>Mages, Hans W.</au><au>Kroczek, Richard A.</au><au>Peter, Hans H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency</atitle><jtitle>Nature immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2003-03-01</date><risdate>2003</risdate><volume>4</volume><issue>3</issue><spage>261</spage><epage>268</epage><pages>261-268</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>No genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the “inducible costimulator” on activated T cells, due to an inherited homozygous deletion in the ICOS gene. T cells from these individuals were normal with regard to subset distribution, activation, cytokine production and proliferation. In contrast, naive, switched and memory B cells were reduced. The phenotype of human ICOS deficiency, which differs in key aspects from that of the ICOS
−/−
mouse, suggests a critical involvement of ICOS in T cell help for late B cell differentiation, class-switching and memory B cell generation.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12577056</pmid><doi>10.1038/ni902</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1529-2908 |
| ispartof | Nature immunology, 2003-03, Vol.4 (3), p.261-268 |
| issn | 1529-2908 1529-2916 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_73060723 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Antigens, Differentiation, T-Lymphocyte - genetics B-Lymphocytes - physiology Biomedical and Life Sciences Biomedicine CD28 Antigens - immunology Cell differentiation Cell Differentiation - immunology Common Variable Immunodeficiency - genetics Homozygote Humans Immunoglobulin A - blood Immunoglobulin G - blood Immunoglobulin M - blood Immunologic Memory - immunology Immunology Inducible T-Cell Co-Stimulator Protein Infectious Diseases Receptors, Antigen, T-Cell - immunology Sequence Deletion T-Lymphocytes - physiology |
| title | Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T06%3A13%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Homozygous%20loss%20of%20ICOS%20is%20associated%20with%20adult-onset%20common%20variable%20immunodeficiency&rft.jtitle=Nature%20immunology&rft.au=Grimbacher,%20Bodo&rft.date=2003-03-01&rft.volume=4&rft.issue=3&rft.spage=261&rft.epage=268&rft.pages=261-268&rft.issn=1529-2908&rft.eissn=1529-2916&rft_id=info:doi/10.1038/ni902&rft_dat=%3Cgale_proqu%3EA188808291%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222753423&rft_id=info:pmid/12577056&rft_galeid=A188808291&rfr_iscdi=true |