Induction therapy with Campath-IH, a humanized anti-CD52 monoclonal antibody depleting T and B lymphocytes, has been used in organ transplantation with the final goal of resetting the immune system in order to promote a tolerance-permissive environment and, at the same time, to reduce the need for chronic maintenance immunosuppression. To explore whether thisO may result from the capability of Campath-IH, in association with different maintenance regimens, to promote regulatory T cells (Treg) expansion and to assess whether this may translate into better graft outcomes in the long-term, 21 renal transplant patients receiving Campath-IH induction were randomized to low-dose SRL (n=ll) or low-dose CsA (n=10), both in addition to low-dose mycophenolate mofetil (MMF) as maintenance immunosuppressive therapy and monitored for over 30 month follow-up. SRL-treated Patients showed an important expansion of circulating CD4⁺CD25highFOXP3⁺ Treg that, at one and two years after transplant, were significantly more abundant than in the CsA group. T cells isolated from peripheral blood long-term post-transplant were hyporesponsive to donor alloantigens in both treatment arms. In SRL-, but not CsA-treated patients, hyporesponsiveness was reversed by Treg depletion. T cells from CsA-treated pattients were anergic to donor antigens. Despite higher Treg counts, SRL-treated patients had a faster GFR and RPF decline, more clinical proteinuria, significantly higher tubular C4d staining score and a trend to higher chronic allograft damage index score, compared to CsA-treated patients. There was no significant correlation between Treg counts and any considered outcome variable in the study group as a whole and within each treatment group.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:499459 |
| Date | January 2009 |
| Creators | Cravedi, Paolo |
| Publisher | Open University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0021 seconds