Effect of immunoadsorptions on acute vascular rejection of HCD55 pig kidneys by baboons
Introduction The definition of the best immunosuppressive protocol to prevent acute vascular rejection (AVR) is still a major issue in xenotransplantation. We have previously studied a protocol associating antibody depletion, immunosuppression and human CD55 (hCD55) transgenic pig organs. Surprisingly, we did not observe any prolongation of graft survival as compared to the non-transgenic controls and the long survivals already described elsewhere without any immunoadsorption (IA). Thus, we developed two new series with or without IA but with an immunosuppression in order to investigate whether IA had a negative impact on the prevention of AVR.
Materials and methods Two groups of baboon recipients of hCD55 transgenic pig kidneys were studied. The first group (n = 4) received an immunosuppressive regimen consisting of an optimized cyclophosphamide treatment (starting on day −1), cyclosporin A, mycophenolate mofetil and corticosteroids, whereas the second group (n = 4) received this same immunosuppression in addition to a pretransplant immunoadsorption using Ig Therasorb columns.
Results None of the immunosuppressed only animals showed any sign of AVR on the day 6 biopsy or even later, however, they died on days 8, 8, 10 and 13, respectively (two of general infection, one of a DIC and one of an unknown cause). In contrast, all immunoadsorbed animals showed signs of AVR at day 5. Immunoadsorption was effective in decreasing levels of both IgM and IgG, however, AVR was associated with an increase in IgM to nearly preimmunoadsorption levels.
Conclusions These results suggest that immunoadsorption of total Ig prior to transplantation could be detrimental to graft survival potentially by depleting beneficial antibodies that could play a role in inhibiting complement activation and inducing graft accommodation. IgM and IgG antibody deposition, complement fixation, markers of accommodation, signs of apoptosis, cellular infiltration and cytokine transcription in biopsies taken from nonrejecting recipients and at rejection from the immunoadsorbed animals is currently underway in order to determine the relative antibody and cellular participation in AVR compared to nonrejecting animals. To further investigate this interesting phenomenon we aim to study additional series with selective anti-Gal and IgM depletion.