Evolution of CMV Antiviral T-cell Immunity Over the Next Six Months Initiation of Treatment With Belatacept. (VIRABEL)

Belatacept inhibits T cell activation by blocking the costimulatory signal. In kidney transplantation, it limits the use of anticalcineurins (1) while ensuring a satisfactory level of immunosuppression.

The Rouen strategy consists of offering belatacept to kidney transplant patients presenting with clinical and biological intolerance to anticalcineurins with histological toxicity. This strategy improves or stabilizes the graft glomerular filtration rate (GFR) in patients with precarious renal function. However, we observed a high incidence of opportunistic infections (12.1%), mainly due to CMV, in elderly patients whose GFR is <25ml/min. 2/3 of CMV infections occur in the year following the introduction of belatacept, can be particularly severe and involve the vital prognosis of the patients as well as that of the graft. They led us to carry out systematic antiviral prophylaxis for 3 months with Valganciclovir as soon as belatacept was introduced.

The immune control of CMV depends essentially on effector/memory T cells specific to the virus. The impact of costimulation blockade on certain persistent viral infections has been studied experimentally. It is major when the infection is established but appears variable in the chronic phase depending on the type of virus. The viral load seems to be an element conditioning the size of the antiviral T lymphocyte repertoire as well as its functions (lymphocyte exhaustion). In the case of CMV, the consequences of costimulation blockade on the pool of specific effector/memory T cells are not known. We hypothesize that under belatacept, the weight of CMV on the immune system induces quantitative changes in the pool of effector/memory T cells (inflation or, on the contrary, contraction) and/or its functional exhaustion, likely to lead to a loss control of viral replication. We therefore propose to study the evolution of the anti-CMV response in terms of amplitude, specificity and functionality, after introduction of belatacept in CMV+ patients.