Presence of anti-FKBP12 autoantibodies in patients with liver allografts: its association with allograft rejection.

Abstract

It was reported that autoantibodies against cyclophilin are present in sera from systemic lupus erythematosus. We hypothesized that autoantibodies against FKBP12, another immunophilin, may be present in the plasma of liver allograft recipients, which may affect the clinical outcome of liver allografts. We investigated the relationship between the presence of anti-FKBP12 autoantibodies and rejection episodes in 47 patients treated with FK506 after living-related partial liver transplantation (LRLT). The patients consisted of two groups: 22 with rejection [R(+) group] and 25 without rejection [R(-) group]. The autoantibodies were measured by an indirect ELISA, and the specificity was confirmed by absorption with antigen and immunoblotting. The autoantibodies were detected in 13 of 22 in the R(+) group (IgG: 5; IgM: 6; both: 2) and in 6 of 25 in the R(-) group (IgG: 2; IgM: 3; both: 1) before LRLT (P=0.0193). After LRLT, they were also detected more frequently in the R(+) group (12 of 22; IgG: 1; IgM: 8; both: 3) than in the R(-) group (2 of 25; IgG: 1; IgM: 1) (P=0.001). In the R(+) group, the mortality of the patients who were positive and negative for the autoantibodies was 6 of 12 and 2 of 10, respectively. The autoantibodies were detected in all four patients with chronic or refractory acute rejection. The autoantibodies were not detected in any of the 34 healthy subjects. These results suggest that the presence of the autoantibodies in patients before transplantation is related to rejection, and the presence after transplantation may be associated with patient outcome.