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 language | English (US) |
|---|---|
| Pages (from-to) | 791-801 |
| Number of pages | 11 |
| Journal | Journal of Infectious Diseases |
| Volume | 180 |
| Issue number | 3 |
| DOIs | |
| State | Published - 1999 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Immunology
Cite this
Monoclonal antibody-mediated toxicity in Cryptococcus neoformans infection : Mechanism and relationship to antibody isotype. / Lendvai, Nikoletta; Casadevall, Arturo.
In: Journal of Infectious Diseases, Vol. 180, No. 3, 1999, p. 791-801.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Monoclonal antibody-mediated toxicity in Cryptococcus neoformans infection
T2 - Mechanism and relationship to antibody isotype
AU - Lendvai, Nikoletta
AU - Casadevall, Arturo
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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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U2 - 10.1086/314946
DO - 10.1086/314946
M3 - Article
VL - 180
SP - 791
EP - 801
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 3
ER -