The addition of sirolimus to cyclosporine and steroids inhibits the anti-equine antibody response in renal transplant recipients treated with antithymocyte globulin

Polyclonal antibodies, such as equine antithymocyte globulin (ATGAM(R)), are known to induce antibody formation. This study evaluated the in vivo effect of sirolimus on antibody formation associated with the use of equine antithymocyte globulin in renal transplant recipients. Recipients of either a living-related donor or cadaveric renal allograft received azathioprine (AZA) (n = 15), mycophenolate mofetill (MMF) (n = 12), or sirolimus (n = 15) in addition to baseline immunosuppression with corticosteroids, cyclosporine, and equine antithymocyte globulin. Immediately before transplantation and weekly for at least 1 month, sequential serum specimens were tested for the presence of human anti-equine antibody using an enzyme-linked immunosorbent assay (ELISA). Anti-equine antibody formation was significantly different among the three treatment groups. Fewer patients receiving MMF (17%, p=0.007 vs. AZA) and sirolimus (13%, P=0.003 vs. AZA) developed anti-equine antibody compared with AZA (66%). There was no significant difference (p=0.81) in the sensitization to equine antithymocyte globulin when comparing the patients receiving MMF or sirolimus. In the sensitized patients, high anti-equine antibody titers (>1:500) were more common in those receiving AZA (n = 3) than MMF (n = 0) or sirolimus (n = 1). Compared to AZA, sirolimus, when given in combination with cyclosporine A, significantly reduced anti-equine antibody formation to a degree similar to MMF.