Monoclonal antibody-mediated toxicity in Cryptococcus neoformans infection

Mechanism and relationship to antibody isotype

Nikoletta Lendvai, Arturo Casadevall

Research output: Contribution to journalArticle

Abstract

Antibody reagents represent an alternative for the therapy of human cryptococcosis, and monoclonal antibody 18B7 (IgG1) is a candidate for phase I trial in humans with cryptococcosis. However, antibody administration to mice with established Cryptococcus neoformans infection has been reported to produce acute lethal toxicity (ALT). The present study confirmed this phenomenon and investigated the mechanism of ALT. ALT was associated with hemoconcentration, hypotension, and circulatory collapse; however, toxicity could be prevented by platelet-activating factor inhibitor, rat antibody to Fc receptor, or IgM before IgG1. Significant isotype-specific differences were found in ALT, which can be interpreted as consistent with the hypothesis that there are distinct Fc receptors for murine IgG1 and IgG3. The IgM and IgG3 isotype preference in antibody responses to polysaccharide antigens in mice may translate to a lack of toxicity of antigen-antibody complexes during the course of infections with encapsulated pathogens.

Original languageEnglish (US)
Pages (from-to)791-801
Number of pages11
JournalJournal of Infectious Diseases
Volume180
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

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Cryptococcus neoformans
Immunoglobulin G
Monoclonal Antibodies
Antibodies
Cryptococcosis
Infection
Fc Receptors
Platelet Activating Factor
Complementary Therapies
Antigen-Antibody Complex
Hypotension
Antibody Formation
Polysaccharides
Immunoglobulin M
Shock
Antigens

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

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abstract = "Antibody reagents represent an alternative for the therapy of human cryptococcosis, and monoclonal antibody 18B7 (IgG1) is a candidate for phase I trial in humans with cryptococcosis. However, antibody administration to mice with established Cryptococcus neoformans infection has been reported to produce acute lethal toxicity (ALT). The present study confirmed this phenomenon and investigated the mechanism of ALT. ALT was associated with hemoconcentration, hypotension, and circulatory collapse; however, toxicity could be prevented by platelet-activating factor inhibitor, rat antibody to Fc receptor, or IgM before IgG1. Significant isotype-specific differences were found in ALT, which can be interpreted as consistent with the hypothesis that there are distinct Fc receptors for murine IgG1 and IgG3. The IgM and IgG3 isotype preference in antibody responses to polysaccharide antigens in mice may translate to a lack of toxicity of antigen-antibody complexes during the course of infections with encapsulated pathogens.",
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