Polyvalent Immunoglobulin Preparations Inhibit Pneumolysin-Induced Platelet Destruction

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

doi:10.1055/a-1723-1880

Cited by 6 publications

(6 citation statements)

References 31 publications

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“…The efficient neutralization of bacterial toxins by IgM, IgA and IgG plasma preparations is known from literature ( 150 , 165 – 169 ), but was also demonstrated for trimodulin. Trimodulin can effectively neutralize pneumolysin and protect platelets from pneumolysin-induced damage ( 192 , 193 ).…”

Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

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Inflammatory lung diseases represent a persistent burden for patients and the global healthcare system. The combination of high morbidity, (partially) high mortality and limited innovations in the last decades, have resulted in a great demand for new therapeutics. Are therapeutic IgA antibodies possibly a new hope in the treatment of inflammatory lung diseases? Current research increasingly unravels the elementary functions of IgA as protector against infections and as modulator of overwhelming inflammation. With a focus on IgA, this review describes the pathological alterations in mucosal immunity and how they contribute to chronic inflammation in the most common inflammatory lung diseases. The current knowledge of IgA functions in the circulation, and particularly in the respiratory mucosa, are summarized. The interplay between neutrophils and IgA seems to be key in control of inflammation. In addition, the hurdles and benefits of therapeutic IgA antibodies, as well as the currently known clinically used IgA preparations are described. The data highlighted here, together with upcoming research strategies aiming at circumventing the current pitfalls in IgA research may pave the way for this promising antibody class in the application of inflammatory lung diseases.

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Section: Iga As Therapeutic Antibodymentioning

confidence: 99%

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Bohländer

2023

Front. Immunol.

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“…This, together with the fact that immunoglobulins have been used since ancient times for the treatment of infectious diseases, makes this strategy very promising. In fact, the effect of PLY on platelets and erythrocytes can be neutralized by polyvalent human IgG and trimodulin [143]. In a clinical trial in patients with S. pneumoniae CAP, treatment with trimodulin (182.6 mg/kg, for 5 consecutive days) improved survival compared to patients treated with placebo [45].…”

Section: Plos Onementioning

confidence: 99%

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

et al. 2023

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Background This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction. Methods The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework. Results Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability. Discussion Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis. Conclusion A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.

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“…Igs can affect platelet activity indirectly. A study showed an influence of Igs on the exotoxin of Streptococcus pneumonia pneumolysin, which causes lysis of erythrocytes and platelets [194,195]. IVIg counteracted pneumolysin-induced lysis of platelets.…”

Section: Nonclinical Studies Investigating the Supporting Role Of Pol...mentioning

confidence: 99%

Multifaceted Tissue-Protective Functions of Polyvalent Immunoglobulin Preparations in Severe Infections—Interactions with Neutrophils, Complement, and Coagulation Pathways

Schmidt,

Weißmüller,

Heinz

2023

Biomedicines

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Severe infections induce immune defense mechanisms and initial tissue damage, which produce an inflammatory neutrophil response. Upon dysregulation of these responses, inflammation, further tissue damage, and systemic spread of the pathogen may occur. Subsequent vascular inflammation and activation of coagulation processes may cause microvascular obstruction at sites distal to the primary site of infection. Low immunoglobulin (Ig) M and IgG levels have been detected in patients with severe infections like sCAP and sepsis, associated with increased severity and mortality. Based on Ig’s modes of action, supplementation with polyvalent intravenous Ig preparations (standard IVIg or IgM/IgA-enriched Ig preparations) has long been discussed as a treatment option for severe infections. A prerequisite seems to be the timely administration of Ig preparations before excessive tissue damage has occurred and coagulopathy has developed. This review focuses on nonclinical and clinical studies that evaluated tissue-protective activities resulting from interactions of Igs with neutrophils, complement, and the coagulation system. The data indicate that coagulopathy, organ failure, and even death of patients can possibly be prevented by the timely combined interactions of (natural) IgM, IgA, and IgG with neutrophils and complement.

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Polyvalent Immunoglobulin Preparations Inhibit Pneumolysin-Induced Platelet Destruction

Cited by 6 publications

References 31 publications

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

A new hope? Possibilities of therapeutic IgA antibodies in the treatment of inflammatory lung diseases

Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review

Multifaceted Tissue-Protective Functions of Polyvalent Immunoglobulin Preparations in Severe Infections—Interactions with Neutrophils, Complement, and Coagulation Pathways

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