Removal of xenoreactive antibodies by protein‐A immunoadsorption: experience in 22 patients

Abstract

The presence of naturally occurring anti-Galalpha1-3Gal (antialphaGal) Ab in human serum is believed to be a major factor in the pathogenesis of hyperacute rejection of discordant organ xenografts such as the pig-to-human combination. Galalpha1-3Gal epitopes are expressed on pig tissues and the binding of anti-Galalpha1-3Gal leads to endothelial cell activation and complement-mediated hyperacute graft rejection. Several strategies have been suggested in donor animals or in the xenograft recipient to overcome the anti-alphaGal barrier. Protein-A immunoadsorption (PAIA) was developed for the in vivo removal of circulating Ab and it has been shown to be effective in cases where pathogenic auto or alloAb are present. The aim of our study was to analyze the effect of PAIA on total and xenoreactive serum anti-alphaGal immunoglobulin levels in a group of patients treated with this technique for different diseases. After three consecutive sessions of PAIA, total and xenoreactive IgG and IgM immunoglobulin levels were decreased by more than 50% of pre-treatment levels. So we conclude that PAIA is an effective method to significantly reduce circulating Ab, including xenogeneic IgM and IgG Ab. This mode of therapy might be considered as a tool to overcome hyperacute xenograft rejection. PAIA combined with other therapeutic approaches may well protect the xenograft.

Characteristics of protein–carbohydrate interactions as a basis for developing novel carbohydrate‐based antirejection therapies

“…Non‐specific extracorporeal immunoadsorption using protein‐A or antihuman immunoglobulin linked to a stationary phase such as Sepharose or silica are also well‐documented techniques used for the removal of ABH‐, HLA‐ and xenoantibodies 106 , 110 , 112 , 113 , 114 , 115 , 116 , 117 . However, all types of antibodies are removed by these techniques, including those acting as the first line of defence against infections, including viruses 25 .…”

Galectin-1 Restores Immune Tolerance to Liver Transplantation Through Activation of Hepatic Stellate Cells

“…The induction of specific immune tolerance has been reported to be a feasible approach to treating organ rejection [21]. Galalpha1-3Gal epitopes were expressed in pig tissues and the binding of anti-Galalpha1-3Gal led to endothelial cell activation and complement-mediated hyperacute graft rejection [22]. Recently, galectin-1 was demonstrated to significantly attenuate allogeneic immune responses in murine LT models [5].…”

Literature update 2000, part 1

“…Therapeutic strategies to prevent hyperacute rejection have included efforts to inhibit anti‐gal antibodies with synthetic galactosyl inhibitors [23], and efforts to absorb the antibodies with columns [24,25]. Dalmasso and colleagues found that pig endothelium up‐regulates expression of CD59 after treatment with a gal‐binding lectin [26].…”