Further insights into the anti-PF4/heparin IgM immune response
Summary Anti-platelet factor 4 (PF4)/heparin antibodies are not only the cause of heparin-induced thrombocytopenia but might also play a role in the antibacterial host defence. Recently, marginal zone (MZ) B cells were identified to be crucial for anti-PF4/heparin IgG antibody production in mice. Co...
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| Veröffentlicht in: | Thrombosis and haemostasis 2016-04, Vol.115 (4), p.752-761 |
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| creator | Krauel, Krystin Schulze, Annika Jouni, Rabie Hackbarth, Christine Hietkamp, Bernhard Selleng, Sixten Koster, Andreas Jensch, Inga Linde, Julia van der Schwertz, Hansjörg Bakchoul, Tamam Hundt, Matthias Greinacher, Andreas |
| description | Summary
Anti-platelet factor 4 (PF4)/heparin antibodies are not only the cause of heparin-induced thrombocytopenia but might also play a role in the antibacterial host defence. Recently, marginal zone (MZ) B cells were identified to be crucial for anti-PF4/heparin IgG antibody production in mice. Combining human studies and a murine model of polymicrobial sepsis we further characterised the far less investigated anti-PF4/heparin IgM immune response. We detected anti-PF4/heparin IgM antibodies in the sera of paediatric patients < 6 months of age after cardiac surgery and in sera of splenectomised mice subjected to polymicrobial sepsis. In addition, PF4/heparin-specific IgM B cells were not only found in murine spleen, but also in peritoneum and bone marrow upon
in vitro
stimulation. Together, this indicates involvement of additional B cell populations, as MZ B cells are not fully developed in humans until the second year of life and are restricted to the spleen in mice. Moreover, PF4/heparin-specific B cells were detected in human cord blood upon
in vitro
stimulation and PF4
-/-
mice produced anti-PF4/heparin IgM antibodies after polymicrobial sepsis. In conclusion, the anti-PF4/heparin IgM response is a potential innate immune reaction driven by a B cell population distinct from MZ B cells.
Supplementary Material to this article is available online at www.thrombosis-online.com. |
| doi_str_mv | 10.1160/TH15-08-0654 |
| format | Article |
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Anti-platelet factor 4 (PF4)/heparin antibodies are not only the cause of heparin-induced thrombocytopenia but might also play a role in the antibacterial host defence. Recently, marginal zone (MZ) B cells were identified to be crucial for anti-PF4/heparin IgG antibody production in mice. Combining human studies and a murine model of polymicrobial sepsis we further characterised the far less investigated anti-PF4/heparin IgM immune response. We detected anti-PF4/heparin IgM antibodies in the sera of paediatric patients < 6 months of age after cardiac surgery and in sera of splenectomised mice subjected to polymicrobial sepsis. In addition, PF4/heparin-specific IgM B cells were not only found in murine spleen, but also in peritoneum and bone marrow upon
in vitro
stimulation. Together, this indicates involvement of additional B cell populations, as MZ B cells are not fully developed in humans until the second year of life and are restricted to the spleen in mice. Moreover, PF4/heparin-specific B cells were detected in human cord blood upon
in vitro
stimulation and PF4
-/-
mice produced anti-PF4/heparin IgM antibodies after polymicrobial sepsis. In conclusion, the anti-PF4/heparin IgM response is a potential innate immune reaction driven by a B cell population distinct from MZ B cells.
Supplementary Material to this article is available online at www.thrombosis-online.com.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/TH15-08-0654</identifier><identifier>PMID: 26467272</identifier><language>eng</language><publisher>Germany: Schattauer GmbH</publisher><subject>Animals ; Antibody Formation ; B-Lymphocytes - immunology ; Cellular Haemostasis and Platelets ; Coinfection - immunology ; Disease Models, Animal ; Female ; Humans ; Immunity, Innate ; Immunoglobulin M - blood ; Infant ; Infant, Newborn ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Platelet Factor 4 - genetics ; Platelet Factor 4 - immunology ; Sepsis - immunology ; Thrombocytopenia - chemically induced ; Thrombocytopenia - immunology</subject><ispartof>Thrombosis and haemostasis, 2016-04, Vol.115 (4), p.752-761</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c327t-9b7172a767a2e1ac8307f700b2b90ddb5c7bd73c1d04d85dd0ae860a0de558383</citedby><cites>FETCH-LOGICAL-c327t-9b7172a767a2e1ac8307f700b2b90ddb5c7bd73c1d04d85dd0ae860a0de558383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/TH15-08-0654.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/TH15-08-0654$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,780,784,3018,27924,27925,54559,54560</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26467272$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krauel, Krystin</creatorcontrib><creatorcontrib>Schulze, Annika</creatorcontrib><creatorcontrib>Jouni, Rabie</creatorcontrib><creatorcontrib>Hackbarth, Christine</creatorcontrib><creatorcontrib>Hietkamp, Bernhard</creatorcontrib><creatorcontrib>Selleng, Sixten</creatorcontrib><creatorcontrib>Koster, Andreas</creatorcontrib><creatorcontrib>Jensch, Inga</creatorcontrib><creatorcontrib>Linde, Julia van der</creatorcontrib><creatorcontrib>Schwertz, Hansjörg</creatorcontrib><creatorcontrib>Bakchoul, Tamam</creatorcontrib><creatorcontrib>Hundt, Matthias</creatorcontrib><creatorcontrib>Greinacher, Andreas</creatorcontrib><title>Further insights into the anti-PF4/heparin IgM immune response</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
Anti-platelet factor 4 (PF4)/heparin antibodies are not only the cause of heparin-induced thrombocytopenia but might also play a role in the antibacterial host defence. Recently, marginal zone (MZ) B cells were identified to be crucial for anti-PF4/heparin IgG antibody production in mice. Combining human studies and a murine model of polymicrobial sepsis we further characterised the far less investigated anti-PF4/heparin IgM immune response. We detected anti-PF4/heparin IgM antibodies in the sera of paediatric patients < 6 months of age after cardiac surgery and in sera of splenectomised mice subjected to polymicrobial sepsis. In addition, PF4/heparin-specific IgM B cells were not only found in murine spleen, but also in peritoneum and bone marrow upon
in vitro
stimulation. Together, this indicates involvement of additional B cell populations, as MZ B cells are not fully developed in humans until the second year of life and are restricted to the spleen in mice. Moreover, PF4/heparin-specific B cells were detected in human cord blood upon
in vitro
stimulation and PF4
-/-
mice produced anti-PF4/heparin IgM antibodies after polymicrobial sepsis. In conclusion, the anti-PF4/heparin IgM response is a potential innate immune reaction driven by a B cell population distinct from MZ B cells.
Supplementary Material to this article is available online at www.thrombosis-online.com.</description><subject>Animals</subject><subject>Antibody Formation</subject><subject>B-Lymphocytes - immunology</subject><subject>Cellular Haemostasis and Platelets</subject><subject>Coinfection - immunology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Humans</subject><subject>Immunity, Innate</subject><subject>Immunoglobulin M - blood</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Platelet Factor 4 - genetics</subject><subject>Platelet Factor 4 - immunology</subject><subject>Sepsis - immunology</subject><subject>Thrombocytopenia - chemically induced</subject><subject>Thrombocytopenia - immunology</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEtLAzEUhYMotlZ3rmX2GnuTyWs2ghTHFiq6qOAuZCZpJ8V5kMws_PdOqbpydQ-XjwPnQ-iawD0hAuabJeEYFAbB2QmaUi4kFir7OEVTSBlgQRmfoIsY9wBEsIyfowkVTEgq6RQ95EPoKxcS30S_q_o4hr5Nxldimt7jt5zNK9eZ4JtktXtJfF0PjUuCi13bRHeJzrbmM7qrnztD7_nTZrHE69fn1eJxjcuUyh5nhSSSGimkoY6YUqUgtxKgoEUG1ha8lIWVaUksMKu4tWCcEmDAOs5VqtIZujv2lqGNMbit7oKvTfjSBPRBgz5o0KD0QcOI3xzxbihqZ__g390jcHsE-sq72ul9O4RmHPB_3Tdyy2TY</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Krauel, Krystin</creator><creator>Schulze, Annika</creator><creator>Jouni, Rabie</creator><creator>Hackbarth, Christine</creator><creator>Hietkamp, Bernhard</creator><creator>Selleng, Sixten</creator><creator>Koster, Andreas</creator><creator>Jensch, Inga</creator><creator>Linde, Julia van der</creator><creator>Schwertz, Hansjörg</creator><creator>Bakchoul, Tamam</creator><creator>Hundt, Matthias</creator><creator>Greinacher, Andreas</creator><general>Schattauer GmbH</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></search><sort><creationdate>20160401</creationdate><title>Further insights into the anti-PF4/heparin IgM immune response</title><author>Krauel, Krystin ; Schulze, Annika ; Jouni, Rabie ; Hackbarth, Christine ; Hietkamp, Bernhard ; Selleng, Sixten ; Koster, Andreas ; Jensch, Inga ; Linde, Julia van der ; Schwertz, Hansjörg ; Bakchoul, Tamam ; Hundt, Matthias ; Greinacher, Andreas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c327t-9b7172a767a2e1ac8307f700b2b90ddb5c7bd73c1d04d85dd0ae860a0de558383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antibody Formation</topic><topic>B-Lymphocytes - immunology</topic><topic>Cellular Haemostasis and Platelets</topic><topic>Coinfection - immunology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Humans</topic><topic>Immunity, Innate</topic><topic>Immunoglobulin M - blood</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Platelet Factor 4 - genetics</topic><topic>Platelet Factor 4 - immunology</topic><topic>Sepsis - immunology</topic><topic>Thrombocytopenia - chemically induced</topic><topic>Thrombocytopenia - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krauel, Krystin</creatorcontrib><creatorcontrib>Schulze, Annika</creatorcontrib><creatorcontrib>Jouni, Rabie</creatorcontrib><creatorcontrib>Hackbarth, Christine</creatorcontrib><creatorcontrib>Hietkamp, Bernhard</creatorcontrib><creatorcontrib>Selleng, Sixten</creatorcontrib><creatorcontrib>Koster, Andreas</creatorcontrib><creatorcontrib>Jensch, Inga</creatorcontrib><creatorcontrib>Linde, Julia van der</creatorcontrib><creatorcontrib>Schwertz, Hansjörg</creatorcontrib><creatorcontrib>Bakchoul, Tamam</creatorcontrib><creatorcontrib>Hundt, Matthias</creatorcontrib><creatorcontrib>Greinacher, Andreas</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krauel, Krystin</au><au>Schulze, Annika</au><au>Jouni, Rabie</au><au>Hackbarth, Christine</au><au>Hietkamp, Bernhard</au><au>Selleng, Sixten</au><au>Koster, Andreas</au><au>Jensch, Inga</au><au>Linde, Julia van der</au><au>Schwertz, Hansjörg</au><au>Bakchoul, Tamam</au><au>Hundt, Matthias</au><au>Greinacher, Andreas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Further insights into the anti-PF4/heparin IgM immune response</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>115</volume><issue>4</issue><spage>752</spage><epage>761</epage><pages>752-761</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><abstract>Summary
Anti-platelet factor 4 (PF4)/heparin antibodies are not only the cause of heparin-induced thrombocytopenia but might also play a role in the antibacterial host defence. Recently, marginal zone (MZ) B cells were identified to be crucial for anti-PF4/heparin IgG antibody production in mice. Combining human studies and a murine model of polymicrobial sepsis we further characterised the far less investigated anti-PF4/heparin IgM immune response. We detected anti-PF4/heparin IgM antibodies in the sera of paediatric patients < 6 months of age after cardiac surgery and in sera of splenectomised mice subjected to polymicrobial sepsis. In addition, PF4/heparin-specific IgM B cells were not only found in murine spleen, but also in peritoneum and bone marrow upon
in vitro
stimulation. Together, this indicates involvement of additional B cell populations, as MZ B cells are not fully developed in humans until the second year of life and are restricted to the spleen in mice. Moreover, PF4/heparin-specific B cells were detected in human cord blood upon
in vitro
stimulation and PF4
-/-
mice produced anti-PF4/heparin IgM antibodies after polymicrobial sepsis. In conclusion, the anti-PF4/heparin IgM response is a potential innate immune reaction driven by a B cell population distinct from MZ B cells.
Supplementary Material to this article is available online at www.thrombosis-online.com.</abstract><cop>Germany</cop><pub>Schattauer GmbH</pub><pmid>26467272</pmid><doi>10.1160/TH15-08-0654</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6245 |
| ispartof | Thrombosis and haemostasis, 2016-04, Vol.115 (4), p.752-761 |
| issn | 0340-6245 2567-689X |
| language | eng |
| recordid | cdi_crossref_primary_10_1160_TH15_08_0654 |
| source | MEDLINE; Thieme Connect Journals |
| subjects | Animals Antibody Formation B-Lymphocytes - immunology Cellular Haemostasis and Platelets Coinfection - immunology Disease Models, Animal Female Humans Immunity, Innate Immunoglobulin M - blood Infant Infant, Newborn Male Mice Mice, Inbred C57BL Mice, Knockout Platelet Factor 4 - genetics Platelet Factor 4 - immunology Sepsis - immunology Thrombocytopenia - chemically induced Thrombocytopenia - immunology |
| title | Further insights into the anti-PF4/heparin IgM immune response |
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