Serum anti-rabbit and anti-horse IgG, IgA, and IgM in kidney transplant recipients

BACKGROUND: The therapeutic efficacy of horse antilymphocyte globulins (ALG) or of rabbit antithymocyte globulins (ATG), used for both the prevention and treatment of allograft rejection has been well documented. However, clinical use of these heterologous antibodies can result in the production of antibodies against horse or rabbit proteins and in the development of serum sickness via circulating immune complexes. METHODS: We studied the production of human IgG, and IgM anti-rabbit and anti-horse globulins, in 240 serum samples from 111 kidney transplant recipients, of whom 89 were treated with ALG or ATG (Mérieux-France) as prophylaxis. RESULTS: Up to 8.9% of the patients had anti-ALG and/or -ATG antibodies before the first transplantation. This proportion increased significantly after. Preimmunization did not appear to be predictive of the occurrence of clinical serum sickness, yet sensitization increased, after transplantation, in up to 71% of the subjects who developed this disorder (P = 0.02). In patients receiving a second transplant, pretransplantation antibody levels were not modified by the immunosuppressive therapy applied. No relationship was found between early rejection and antiglobulin antibodies. CONCLUSIONS: Serum anti-rabbit and/or -horse antibodies were demonstrated in a significant proportion of kidney recipients, even before transplantation, possibly due to environmental exposure. A classical pattern of IgM increase was observed when the patients developed an immune response to ALG or ATG, and an IgA response after ALG. These results suggest that patients receiving ALG/ATG should be monitored for the production of anti-ALG/ATG immunoglobulins.