Interaction of anti-HLA antibodies with pig xenoantigens

Background. Many patients with renal failure are condemned to long-term dia lysis with little prospect of transplantion because they are highly sensiti zed with immunoglobulin G (IgG;) directed against class I human leukocyte a ntigens (HLA) of virtually all donors. Xenotransplantation could represent an attractive solution providing their alloantibodies (alloAb) do not recog nize porcine motifs, Hitherto there has been no in vivo demonstration of an y cross;reactivity and the objective of this work was to investigate this p roblem using a technique of extracorporeal pig kidney perfusion as a model of clinical xenografting, Methods. Pig kidneys were perfused ex vivo with plasma from both a group of highly sensitized patients and healthy individuals. Sequential plasma samp les were analyzed for the titer of anti-Gal alpha 1-SGal antibody (Ab) (maj or natural xenoreactive (Ab) by enzyme-linked immunosorbent assay and anti- HLA class I Ab against a cell panel. At the end of perfusion, kidneys were perfused with a citric acid buffer to elute bound Results. Gal alpha 1-3Gal Ab were shown to decrease rapidly in the plasma t in less than 10 min) and then reached a plateau, A fractional decrease in a nti-HLB Ab was also found in some of the perfused plasma samples. Anti-Gal Ab were readily detected in all citric acid perfusates and anti-HLA Ab in 8 of 10, The HLA specificities of eluted Ab were mainly concordant, with the originally designated specificities for each patient, Conclusion, Anti-HLA class I Ah presumably crossreact with pig class I homo logues, However, some plasma samples did not cross-react, suggesting that n egatively cross-matched pig kidneys could be identified in the pig populati on for xenotransplantation In these patients. Further studies are required to precisely describe these cross-reactivities and to understand their func tional significance in xenotransplantation.