Belatacept, a fusión protein that blocks the B7-CD28 costimulation pathway, decreases the level of antibodies in non-human primates and murine models but, few studies have focalized in humans. In the present study we analyzed and compared the levels of APRIL (a factor that play a role in plasma cell activation and survival) in patients with maintenance immunosuppressive therapy with belatacept+MMF vs tacrolimus+MMF+steroids or rapamycin+MMF+steroids.

The population studied was of 10 healthy volunteers and 45 kidney transplanted stable patients treated with belatacept (n= 14), rapamycin+MMF+steroids (n= 15) and tacrolimus+MMF+steroids (n= 16). Figure 1A shows that patients treated with rapamycin+MMF+steroids had the highest plasma levels of APRIL, followed by tacrolimus+MMF+steroids, while belatacept treated patients showed comparable levels to those of healthy subjects regardless the time of the determination after drug infusion. Therefore we hypothesized that belatacept generates a microenvironment less prone to activate plasmablast and plasma cells and, probably thus, reduces the rate of production of antibodies. Then we examined the HLA antibodies in patients that suffered of ABMR, after the incorporation of belatacept (5 mg/kg/dose) to the maintenance immunosuppressive treatment. Figure 2 shows that most of the patients decreased the MFI of HLA class I and II antibodies measured by Luminex at 3, 6 and 12 month post belatacept treatment.

Overall these data shows that belatacept treated patients are less prone to activate plasma cells, and thus maintaining low levels of antibodies, probably due to low levels APRIL.

CITATION INFORMATION: Rial M, Ambrosi N, Caro F, Curcio D, Salaberry J, Guardia O, Dotta A, Guerrieri D, Padros K, Chuluyan E, Casadei D. Patients Treated with Belatacept Show Low Levels of APRIL and HLA Antibodies. Am J Transplant. 2016;16 (suppl 3).

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