title: The addition of sirolimus to cyclosporine and steroids inhibits the anti-equine antibody response in renal transplant recipients treated with antithymocyte globulin.
abstract: Polyclonal antibodies, such as equine antithymocyte globulin (ATGAM), 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 mofetil (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.
authors.affiliation: Departments of Surgery and Microbiology/Immunology, Indiana University, Indianapolis, IN 46202, USA. mpescov@iupui.edu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: Benita K
authors.initials: BK
authors.lastname: Book
authors.forename: Sharon
authors.initials: S
authors.lastname: Henson
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Leapman
authors.forename: Martin L
authors.initials: ML
authors.lastname: Milgrom
authors.forename: Jess
authors.initials: J
authors.lastname: Kimball
authors.forename: Douglas
authors.initials: D
authors.lastname: Norman
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Filo
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000906:Antibodies / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D016572:Cyclosporine / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016030:Kidney Transplantation; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage*
chemical_list: D000305:Adrenal Cortex Hormones; D000906:Antibodies; D000961:Antilymphocyte Serum; D016572:Cyclosporine; D020123:Sirolimus