title: Heme-Exposed Pooled Therapeutic IgG Improves Endotoxemia Survival.
abstract: Antibody repertoires of healthy humans and animals contain a fraction of antibodies able to acquire additional polyspecificity following exposure to several biologically relevant redox molecules (free heme, reactive oxygen species, ferrous ions, HOCl, etc.). The physiological role of these "hidden" polyspecific antibodies is poorly understood. Similar to inherently polyspecific antibodies, those with induced polyspecificicty may also have immunoregulatory properties. We have previously shown that a pooled human IgG preparation, modified by the exposure to ferrous ions, acquires the ability to significantly improve survival of animals with polymicrobial sepsis or aseptic systemic inflammation induced by bacterial lipopolysaccharide or zymosan administration. In the present study, we have analyzed the effects of administration of heme-exposed pooled human IgG in the same models of sepsis and aseptic systemic inflammation. The administration of a single dose of heme-exposed pooled IgG has resulted in a significant increase in the survival of mice with endotoxinemia, but not in those with polymicrobial sepsis and zymosan-induced severe generalized inflammation. Finally, we have provided evidence that the anti-inflammatory effect of heme-exposed IgG can be explained by scavenging of pro-inflammatory mediators.
authors: Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, 1113, Bulgaria. djoumer@microbio.bas.bg.
authors: Iglika
authors: http://orcid.org/0000-0002-4896-9908
authors: I
authors: Djoumerska-Alexieva
authors: UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, F-75006, Paris, France.|INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Université Paris Descartes, F-75006, Paris, France.
authors: Lubka T
authors: LT
authors: Roumenina
authors: Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, 1113, Bulgaria.
authors: Tsvetanka
authors: T
authors: Stefanova
authors: Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, 1113, Bulgaria.
authors: Tchavdar
authors: T
authors: Vassilev
authors: UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, UPMC Univ Paris 06, F-75006, Paris, France.|INSERM, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France.|Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Université Paris Descartes, F-75006, Paris, France.
authors: Jordan D
authors: JD
authors: Dimitrov
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000918:Antibody Specificity; D019446:Endotoxemia / Q000188:drug therapy* / Q000401:mortality; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000187:drug effects / Q000276:immunology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051379:Mice; D018805:Sepsis / Q000188:drug therapy*; D015996:Survival Rate
chemical_list: D000893:Anti-Inflammatory Agents; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D006418:Heme
keywords: IVIg; antibody polyspecificity; heme; passive immunotherapy; sepsis