Autoantibody against fibroblasts in renal transplant recipients: analysis by 51Cr-release assays

In testing for donor-specific alloantibody in renal transplantation we discovered that sera of many recipients lysed their own fibroblasts in complement-dependent cytotoxicity. The incidence of this autoreactivity before and during the first month post-transplant was 15 and 10% respectively, but rose to 48% after 2 months. There was a significant association between autoantibody formation and the presence of donor-specific alloantibody, but no association between autoantibody and graft survival. Autoantibody reactive with fibroblasts was three times more frequent than lymphocytotoxic autoantibody, and showed no association with the presence of such antibody, indicating that these autoantibodies were directed against different antigens. Reduction with 2-mercaptoethanol indicated that much of the autoreactivity was IgM. By absorption tests the autoantigen was shown to be expressed extensively on fibroblasts, but not on lymphocytes, platelets or red cells. Susceptibility to lysis by the autoantibody varied from day to day in the fibroblasts of a particular individual, and also varied from individual to individual. These results are of interest because they indicate that autoantibody formation in human renal allografts may result from chronic allogeneic stimulation, and that the antibody may be detecting a previously unknown fibroblast antigen.