Cross-reactivity studies of horse, goat and rabbit anti-lymphocyte globulin.

In the sera of ten normal humans and twenty-eight candidates for organ transplantation, the passive haemagglutination test detected a 50% incidence of preformed antibodies of low titre directed against horse serum. Such antibodies were also found to cross react with goat or rabbit sera in most instances. Seventeen of the organ recipients were later studied after the institution of treatment with horse antihuman-lymphocyte globulin (ALG). The incidence of anti-horse-serum antibodies rose to 100%. At the same time, an increased activity against goat serum developed; cross-reactions against rabbit serum were also demonstrated but to a less pronounced degree. With immunoelectrophoresis and Ouchterlony diffusion tests, it was shown that the cross-reactivity was to similar although not necessarily identical protein components of the different heterologous sera. These data suggest that there is an inherent risk in switching from one ALG to another, particularly if horse and goat derivatives are used sequentially. Since rabbit ALG does not cross react so extensively with horse or goat serum it would be predicted to be a relatively safer second-line agent. These expectations seemed to have been realized in six patients who were given more than one kind of ALG, always beginning with horse globulin. When goat ALG was administered second, anaphylactic reactions tended to appear early, but when the rabbit product was given second or third, it was relatively well tolerated.