Further insights into the anti-PF4/heparin IgM immune response

Krystin Krauel; Annika Schulze; Rabie Jouni; Christine Hackbarth; Bernhard Hietkamp; Sixten Selleng; Andreas Koster; Inga Jensch; Julia van der Linde; Hansjörg Schwertz; Tamam Bakchoul; Matthias Hundt; Andreas Greinacher

doi:10.1160/TH15-08-0654

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2016; 115(04): 752-761
DOI: 10.1160/TH15-08-0654

Cellular Haemostasis and Platelets

Schattauer GmbH

Further insights into the anti-PF4/heparin IgM immune response

Krystin Krauel^*

¹Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

²Zentrum für Innovationskompetenz - Humorale Immunreaktionen bei kardiovaskulären Erkrankungen, Universität Greifswald, Germany

,

Annika Schulze^*

²Zentrum für Innovationskompetenz - Humorale Immunreaktionen bei kardiovaskulären Erkrankungen, Universität Greifswald, Germany

,

Rabie Jouni

¹Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

,

Christine Hackbarth

¹Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

³Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Universität Greifswald, Germany

,

Bernhard Hietkamp

,

Sixten Selleng

¹Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

,

Andreas Koster

⁴Institut für Anästhesiologie, Herz und Diabetes Zentrum NRW, Bad Oeynhausen, Ruhr-Universität Bochum, Germany

,

Inga Jensch

²Zentrum für Innovationskompetenz - Humorale Immunreaktionen bei kardiovaskulären Erkrankungen, Universität Greifswald, Germany

,

Julia van der Linde

³Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Universität Greifswald, Germany

,

Hansjörg Schwertz

¹Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

⁵Lichtenberg-Professor for Experimental Hemostasis, University of Utah, Salt Lake City, Utah, USA

⁶Program in Molecular Medicine, University of Utah, Salt Lake City, Utah, USA

⁷Department of Surgery, University of Utah, Salt Lake City, Utah, USA

,

Tamam Bakchoul

¹Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

,

Matthias Hundt

²Zentrum für Innovationskompetenz - Humorale Immunreaktionen bei kardiovaskulären Erkrankungen, Universität Greifswald, Germany

,

Andreas Greinacher

¹Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany

› Author Affiliations

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.

Keywords

HIT - anti-PF4/heparin antibodies - B cells - immune response

Full Text

References

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Supplementary Material

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