Polyvalent Immunoglobulin Preparations Inhibit Pneumolysin-Induced Platelet Destruction

Friederike Wiebe; Stefan Handtke; Jan Wesche; Annabel Schnarre; Raghavendra Palankar; Martina Wolff; Kristin Jahn; Franziska Voß; Sabrina Weißmüller; Jörg Schüttrumpf; Andreas Greinacher; Sven Hammerschmidt

doi:10.1055/a-1723-1880

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany

,

Stefan Handtke

¹Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany

,

Jan Wesche

¹Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany

,

Annabel Schnarre

¹Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany

,

Raghavendra Palankar

¹Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany

,

Martina Wolff

¹Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany

,

Kristin Jahn

²Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Germany

,

Franziska Voß

²Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Germany

,

Sabrina Weißmüller

³Department of Research and Development, Biotest AG, Dreieich, Germany

,

Jörg Schüttrumpf

³Department of Research and Development, Biotest AG, Dreieich, Germany

,

Andreas Greinacher

¹Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Germany

,

Sven Hammerschmidt

²Department of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Germany

› Author Affiliations

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

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References

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Supplementary Material

Supplementary Material