Xenotransplantation--state of the art.

Axel Kornerup Hansen,Ejvind Kemp,Dorte Bratbo Sørensen,Kirsten Dahl,Svend Kirkeby

doi:10.1186/1751-0147-45-s1-s7

Axel Kornerup Hansen, Ejvind Kemp + Show 3 more

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https://doi.org/10.1186/1751-0147-45-s1-s7

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Abstract

Rejections caused by xenotransplantation Transplantation between two different species may give rise to two types of graft rejection. Between so-called discordant species a hyperacute rejection (HAR) occurs within minutes or hours. In so-called concordant species this type of rejection does not occur, but over days a delayed xenograft rejection (DXG) (6) will occur. In all transplanted organs, xenoas well as allotransplanted, chronic graft rejection (CRG) will occur after years. Man is concordant with old world primates, but due to several reasons, such as breeding difficulties, risk of retroviral epidemics, concerns for the use of endangered species, etc., the discordant pig is considered the donor of choice. HAR is primarily caused by initiation of the complement cascade. The antigen known to be activating the classical pathway is the alpha-gal epitope (10) (Figure 1); the epitope alternative to the primate AB0 blood group system in most non-primate mammals. In species, in which the antigen is absent, circulating antibodies are present. In humans IgG against the alpha-gal epitope counts for up to a total of 1% of circulating IgG (11). These antibodies probably derive from a reaction to members of the intestinal flora, especially Enterobacteriaceae spp., but also other types of infectious agents possess the alpha-gal epitope as a structural element in their cell walls (10).

Highlights

Strategies to prevent rejection Acute rejections after allotransplantation are generally prevented by immunosuppressive treatment, but HAR may be prevented by cobra snake venom [12] and certain complement regulatory immunocomponents [27], it seems unlikely that complement cascade activation can be prevented by the same means without seriously interfering with the health and well-being of the recipient
Cells of H-transferase transgenic animals show higher resistance towards human sera [20, 28], but in the mice produced by Chen and coworkers [5], it was found that the alpha-gal epitope was only eliminated in those cells, in which it was low in nontransgenic mice
Tn and Forssman, may even become exposed on the cellular wall, which may increase the risk of DXG of organs from a Htransferase transgenic donor [23]. This reduces the likelihood of such a transgenic animal becoming a future xenograft donor

Summary

Introduction

Strategies to prevent rejection Acute rejections after allotransplantation are generally prevented by immunosuppressive treatment, but HAR may be prevented by cobra snake venom [12] and certain complement regulatory immunocomponents [27], it seems unlikely that complement cascade activation can be prevented by the same means without seriously interfering with the health and well-being of the recipient. Cells of H-transferase transgenic animals show higher resistance towards human sera [20, 28], but in the mice produced by Chen and coworkers [5], it was found that the alpha-gal epitope was only eliminated in those cells, in which it was low in nontransgenic mice. The mechanisms behind this are not fully known, but lectin binding studies show that the structure of the cell walls of H-transferase transgenic animals is changed far beyond the sole deficit of the alpha-gal epitope and presence of the H antigen.

Results

Conclusion