Authors:
S. Rautenbach (Cape Town, ZA)
F. Little (Cape Town, ZA)
M. Marszalek (Badalona, ES)
S. Silva-Arrieta (Badalona, ES)
C. Brander (Badalona, ES)
G. Gómez (Barcelona, ES)
M. Bofill (Barcelona, ES)
A. Sanchez (Barcelona, ES)
E. Müller (Cape Town, ZA)
C. Gray (Cape Town, ZA)
Since 2008, 42 renal transplants have been performed from HIV+ deceased donors to HIV+ recipients with renal failure due to HIV associated nephropathy. Despite transplantation across HLA mismatches, these transplants have been relatively rejection-free, safe and successful in a 3-5 year follow-up. Anti-thymocyte globulin (ATG), as a conditioning regimen given immediately post transplant for 5 days, is known to deplete the majority of T-cells, B-cells, macrophages, monocytes, and dendritic cells. Recipients also receive maintenance immunosuppression of prednisone, mycophenolate mofetil and tacrolimus. The impact of ATG and immunosuppression along with transplantation on host inflammatory and regulatory cytokines was assessed to gain insight into immune homeostatic mechanisms after ATG treatment. Despite the HLA mismatches, there were no rejection events, losses of graft function or deaths at 1 year PT. CD4 counts at transplant had a wide range (132 – 973 cells/ml) but did not change significantly over the first year PT. All recipients are adherent to their combined anti-retroviral therapy (cART) and all viral loads were undetectable throughout follow-up, indicating effective anti-retroviral treatment. In a sub group of 10 participants, the Luminex 200 system was used to measure the concentrations of 37 cytokines in plasma immediately pre-transplant and then at 1, 3, 6 and 12 weeks post-transplant. In all these recipients, when compared to baseline, IL-35 significantly decreased at 1, 3, 6 and 12-weeks post-transplant, whilst IL-10 increased significantly at 1-week post-transplant in 5 recipients. Hierarchical clustering showed a decrease over time in IL-35, IFN-g, IL-20, IL-28A, and IL-11 for all assayed participants. This analysis showed that both inflammatory and regulatory cytokines decline over the 12 weeks of follow-up, although IL-10 is transiently increased after ATG treatment, suggestive of induction of an immune regulatory environment. In this environment, the organ recipients tolerate their grafts and have stable HIV suppression in the presence of cART.