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Drug Hypersensitivity Reactions and Pseudoallergy: A Moving Frontline in Allergy...
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Drug Hypersensitivity Reactions and Pseudoallergy: A Moving Frontline in Allergy Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 13050

Special Issue Editor

Dr. János Szebeni

E-Mail Website
Guest Editor
Nanomedicine Research and Education Center, Semmelweis University, 1089 Budapest, Hungary
Interests: hypersensitvity reactions; anaphylaxis; pseudoanaphylaxis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Pseudo-allergy is an acute allergy syndrome manifesting itself in the same clinical symptoms as allergy, but the reactions are not IgE-mediated. In addition to the nonimmune-mediated release of mediators from mast cells and/or basophils, a frequent cause of pseudo-allergy is IgG and IgM binding to the allergen with subsequent complement activation and stimulation of allergy-mediating immune cells via anaphylatoxin and other surface receptors. Pseudo-allergy has become a major issue in modern pharmacotherapy, as the number of unpredicted pseudo-allergic hypersensitivity reactions to state-of-art biologicals and nanomedicines far outweigh the occurrence of true allergic reactions, which can be predicted and diagnosed by classic allergy tests. At present, the standard care against pseudo-allergy, whose worst manifestation is life-threatening pseudo-anaphylaxis, is premedication of patients with antihistamines, steroids, and non-steroidal anti-inflammatory agents. However, this therapy is frequently ineffective, presenting a clinical need for better prevention and/or treatment protocols. A recent development in this field is that the increased occurrence of allergic reactions to some COVID-19 vaccines actually represent a pseudo-allergy. This volume provides a collections of original research papers and reviews on these poorly understood acute reactions, written by clinicians and immunologists encountering this problem. Since IJMS is a journal of molecular science, pure clinical studies will not suitable for our journal. However, clinical or pure model submissions with biomolecular experiments are welcomed.

Dr. János Szebeni
Guest Editor

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Keywords

  • Ig-E-mediated allergy
  • type-I allergy
  • antibodies complement
  • CARPA
  • mast cells
  • histamine
  • IgG
  • IgM
  • IgE
  • hypersensitvity reactions
  • anaphylaxis
  • pseudo-anaphylaxis

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Published Papers (2 papers)

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Research

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17 pages, 2483 KiB  
Article
mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions
by Tamás Bakos, Tamás Mészáros, Gergely Tibor Kozma, Petra Berényi, Réka Facskó, Henriette Farkas, László Dézsi, Carlo Heirman, Stefaan de Koker, Raymond Schiffelers, Kathryn Anne Glatter, Tamás Radovits, Gábor Szénási and János Szebeni
Int. J. Mol. Sci. 2024, 25(7), 3595; https://doi.org/10.3390/ijms25073595 - 22 Mar 2024
Cited by 9 | Viewed by 9553
Abstract
A small fraction of people vaccinated with mRNA–lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the [...] Read more.
A small fraction of people vaccinated with mRNA–lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1β, and TNF-α, suggesting C-dependence of these cytokines’ induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents. Full article
(This article belongs to the Special Issue Drug Hypersensitivity Reactions and Pseudoallergy: A Moving Frontline in Allergy Research)
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Review

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17 pages, 478 KiB  
Review
Balancing Benefits and Risks: A Literature Review on Hypersensitivity Reactions to Human G-CSF (Granulocyte Colony-Stimulating Factor)
by Roxana Silvia Bumbăcea, Mihaela Ruxandra Udrea, Selda Ali and Violeta Claudia Bojincă
Int. J. Mol. Sci. 2024, 25(9), 4807; https://doi.org/10.3390/ijms25094807 - 28 Apr 2024
Cited by 5 | Viewed by 2312
Abstract
Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to [...] Read more.
Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence. Full article
(This article belongs to the Special Issue Drug Hypersensitivity Reactions and Pseudoallergy: A Moving Frontline in Allergy Research)
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