IgG1 protects against IgG3 immune complex mediated renal disease. (176.21)
| Autor: | Richard Strait, Ashley Mahler, Nathaniel Barasa, Keith Stringer, David Witte, Andrew Herr, Fred Finkelman |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:176.21-176.21 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.176.21 |
| Popis: | Immunoglobulins (Ig) have been reported to inhibit or activate effector mechanisms with varying potency. In the mouse, IgG1 has less ability to activate complement (C), interact with stimulatory Fc receptors (FcRs) or form large immune complexes (IC) than other Ig isotypes. Therefore, we hypothesized that IgG1 might suppress IC immunopathology mediated by other isotypes. Consistent with this hypothesis, IgG1-deficient, but not IgG1-sufficient, mice developed renal failure at the time of the peak antibody response when immunized with a potent antigen. Renal disease was both C- and stimulatory FcR-independent, resulted from IgG3 IC cryoglobulin obstruction of glomerular capillaries and usually caused death within 2 weeks. Disease was prevented by administration of antigen-specific IgG1. A passive model of this obstructive glomerulopathy was induced by administration of a TNP-protein conjugate plus IgG3 anti-TNP mAb but not IgG1, IgG2a or IgG2b anti-TNP mAb. IgG3-dependent renal disease could be prevented by co-administration of IgG1, but not IgG2a or IgG2b anti-TNP mAb. These observations demonstrate the adaptive significance of Ig isotypes that poorly activate effector mechanisms and reveal an IC-dependent, complement- and stimulatory FcR-independent mechanism that can rapidly destroy renal structure and function. Our results suggest the possibility of using Ig isotypes that poorly activate effector mechanisms to inhibit IC-induced immunopathology. |
| Databáze: | OpenAIRE |
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