Use of a soluble RT1A(a)/IgG chimeric molecule to prevent the cytotoxic effects of preformed anti-donor antibodies

Scherer, Marcus N. and Graeb, C. and Knechtle, Stuart J. and Jauch, Karl-Walter and Geissler, Edward K. (1999) Use of a soluble RT1A(a)/IgG chimeric molecule to prevent the cytotoxic effects of preformed anti-donor antibodies. LANGENBECKS ARCHIVES OF SURGERY. pp. 423-426. ISSN 1435-2443,

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Abstract

Background: Currently there is no reliable treatment for hyperacute rejection in presensitized patients. The problem with transplanting an organ to a recipient with preformed anti-donor antibodies is that the organ is at a high risk for destruction via complement-mediated cell cytotoxicity. Unfortunately, the list of presensitized patients is growing, since relatively long or indefinite waiting periods for a compatible organ are common. Methods: To address this problem we have initiated experiments in the rat system to attempt to block anti-donor antibodies with a genetically engineered soluble chimeric MHC class I/IgG molecule. The divalent rat MHC class I-like molecule consists of RT1.A(a) extracellular domains (alpha 1 - alpha 3) bound to each of the two variable regions of an intact IgG1 heavy-chain. Restults: Here we show, using complement-mediated cell cytotoxicity assays, that nanomolar concentrations of purified soluble RT1.A(a)/IgG chimeric molecules were able to greatly reduce the cytotoxic effects of serum containing high concentrations of anti-RT1.A(a) antibody. Conclusions: These results suggest that chimeric MHC class I/IgG molecules may be potentially useful to neutralize the damaging effects of anti-donor antibody in presensitized recipients.

Item Type: Article
Uncontrolled Keywords: ;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Nov 2022 09:53
Last Modified: 30 Nov 2022 09:53
URI: https://pred.uni-regensburg.de/id/eprint/48688

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