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CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(07): 1147-1158
DOI: 10.1055/a-1723-1880
Blood Cells, Inflammation and Infection

Polyvalent Immunoglobulin Preparations Inhibit Pneumolysin-Induced Platelet Destruction

Friederike Wiebe
1   Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany
,
Stefan Handtke
1   Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany
,
Jan Wesche
1   Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany
,
Annabel Schnarre
1   Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany
,
Raghavendra Palankar
1   Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany
,
Martina Wolff
1   Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany
,
Kristin Jahn
2   Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Germany
,
Franziska Voß
2   Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Germany
,
Sabrina Weißmüller
3   Department of Research and Development, Biotest AG, Dreieich, Germany
,
Jörg Schüttrumpf
3   Department of Research and Development, Biotest AG, Dreieich, Germany
,
Andreas Greinacher
1   Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany
,
Sven Hammerschmidt 
2   Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Germany
› Author Affiliations Funding This study was funded by Deutsche Forschungsgemeinschaft, Grant/Award Number: Projektnummer 374031971-TRR240; Research support by Biotest. CAPNETZ is supported by the German Center for Lung Research (DZL).
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Abstract

Platelets play an important role in the development and progression of respiratory distress. Functional platelets are known to seal inflammatory endothelial gaps and loss of platelet function has been shown to result in loss of integrity of pulmonary vessels. This leads to fluid accumulation in the pulmonary interstitium, eventually resulting in respiratory distress. Streptococcus pneumoniae is one of the major pathogens causing community-acquired pneumonia. Previously, we have shown that its major toxin pneumolysin forms pores in platelet membranes and renders them nonfunctional. In vitro, this process was inhibited by polyvalent intravenous immunoglobulins (IVIGs). In this study, we compared the efficacy of a standard IVIG preparation (IVIG, 98% immunoglobulin G [IgG]; Privigen, CSL Behring, United States) and an IgM/IgA-enriched immunoglobulin preparation (21% IgA, 23% IgM, 56% IgG; trimodulin, Biotest AG, Germany) to inhibit pneumolysin-induced platelet destruction. Platelet destruction and functionality were assessed by flow cytometry, intracellular calcium release, aggregometry, platelet viability, transwell, and flow chamber assays. Overall, both immunoglobulin preparations efficiently inhibited pneumolysin-induced platelet destruction. The capacity to antagonize pneumolysin mainly depended on the final IgG content. As both polyvalent immunoglobulin preparations efficiently prevent pneumolysin-induced platelet destruction and maintain platelet function in vitro, they represent promising candidates for clinical studies on supportive treatment of pneumococcal pneumonia to reduce progression of respiratory distress.

Keywords

immunoglobulins - platelets - pneumolysin - pneumonia - Streptococcus pneumoniae

Supplementary Material



Publication History

Received: 14 August 2021

Accepted: 10 November 2021

Accepted Manuscript online:
16 December 2021

Article published online:
08 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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