Belatacept inhibits T cell activation by blocking the costimulatory signal. In kidney transplantation, it limits the use of anticalcineurins while ensuring a satisfactory level of immunosuppression.
The Rouen strategy consists of offering belatacept to kidney transplant patients with clinical and laboratory intolerance to anticalcineurins with histological toxicity. This strategy improves or stabilizes the graft's glomerular filtration rate (GFR) in patients with poor renal function. However, a high incidence of opportunistic infections (12.1%), mainly due to CMV, has been observed in elderly patients with a GFR less than 25 ml/min. Two-thirds of CMV infections occur within one year of belatacept initiation and can be particularly severe and life-threatening for both patients and the graft. These results led to the implementation of systematic 3-month antiviral prophylaxis with valganciclovir upon the introduction of belatacept. CMV immune control depends primarily on virus-specific effector/memory T cells. The impact of costimulation blockade on certain persistent viral infections has been studied experimentally. It is significant when the infection is established, but appears variable in the chronic phase depending on the virus type. Viral load appears to be a determining factor in the size of the antiviral T cell repertoire and its functions (lymphocyte exhaustion). In the case of CMV, the consequences of blocking costimulation on the specific effector/memory T cell pool are unknown. The hypothesis of this project is that, under belatacept, the influence of CMV on the immune system induces quantitative changes in the effector/memory T cell pool (inflation or, conversely, contraction) and/or functional exhaustion, likely leading to a loss of control of viral replication. This study therefore proposes to investigate the evolution of the anti-CMV response in terms of amplitude, specificity, and functionality, after the introduction of belatacept in CMV-positive patients.
Study Type
OBSERVATIONAL
Enrollment
28
Switching from anticalcineurins to belatacept in a cohort of kidney transplant recipients seropositive for CMV
University Rouen Hospital
Rouen, France
To study the quantitative changes in anti-CMV T-lymphocyte immunity to the IE-1 antigen within 6 months of a switch from anticalcineurin treatment to belatacept in a cohort of kidney transplant recipients seropositive for CMV
Number of interferon gamma-producing T lymphocytes in response to the IE-1 antigen determined by ELISPOT at M0, M3 and M6.
Time frame: 6 months
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