Antibody Mediated Rejection in Pig-To-Nonhuman Primate Xenotransplantation Models

Authors: Cozzi, Emanuele; Severo, Michela; Bosio, Erika; Besenzon, Federica; Ancona, Ermanno

Source: Current Drug Targets - Cardiovascular & Hematological Disorders, Volume 5, Number 3, June 2005 , pp. 233-253(21)

Publisher: Bentham Science Publishers

Abstract:

Antibody-mediated mechanisms are central to the rejection that occurs when pig organs are transplanted into primates. In this article, the histopathological features of the humoral rejection process in these species combinations, namely hyperacute rejection and acute humoral xenograft rejection, will be illustrated. The profile of the natural and elicited antibodies involved will also be discussed. It has now been demonstrated that the natural immune response to a porcine xenograft is primarily directed to Gal1-3Gal (Gal) specificities, whilst the elicited immune response is directed to both Gal and non-Gal antigens. The principal characteristics of anti-Gal, anti-non-aGal and polyreactive antibodies will be described, together with the identification of the molecules recognised by natural and elicited xenoreactive antibodies. The role of the humoral immune response in the rejection of porcine islets in the primate is still uncertain and the current views on the subject will be discussed. Finally, a concise but comprehensive review of the different strategies that have been attempted to prevent the onset of antibody-mediated rejection is presented. These strategies encompass approaches aimed at interfering with the binding of xenoreactive antibodies with their targets, the use of conventional or novel immunosuppressants and splenectomy. It is undeniable that significant progress has been recently achieved in understanding the humoral rejection process of pig organs transplanted into primates. It is expected that a more comprehensive elucidation of the mechanisms underlying accommodation and tolerance may, in the not too distant future, further extend survival of pig organs transplanted into primates.

Keywords: xenotransplantation; antibody; rejection; pancreatic islets; transgenic pigs; primates; humoral rejection; immunosuppression

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568006054064799

Affiliations: 1: Department of Medical and Surgical Sciences, Clinica Chirurgica III, Via Giustiniani, 2, 35128 Padova, Italy.

Publication date: 2005-06-01

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