Immunoglobulin class and specificity of lymphocytotoxic antibodies after kidney transplantation

The immunoglobulin class and specificity of the cytotoxic antibodies were investigated in sera collected during the first weeks following transplantation from 35 patients with functioning and 20 patients with failed grafts. No patient had had cytotoxic antibodies before the transplant, but 71.5% (25 of 35) of patients with functioning and 75% (15 of 20) of patients with failed graft subsequently developed them. The addition of dithiothreitol, which digests IgM antibodies, resulted in the disappearance of cytotoxicity in all positive sera from patients with a functioning graft. However, in the patients with failed grafts, the immunoglobulin class of the antibody varied; seven patients had only IgM antibodies, and seven had both IgM and IgG. After graft nephrectomy, IgG antibodies appeared in another six patients. In five of six patients with functioning grafts, mouse monoclonal antibodies blocked the cytotoxic activity; four with HLA-DQ monoclonal antibodies (Leu 10), one with HLA Class I (GD5). In the patients with failed grafts, blocking was seen in all nine patients studied; eight by GD5, six by Leu 10, and two by a monoclonal antibody to a monomorphic determinant of HLA-DR (100/77). Although the frequency of antibody-positive patients was similar in the successful and failed groups, the immunoglobulin class of the antibodies developed was IgM in the former group, whereas in the latter group some were IgM and others were IgG. Characterisation of the antibodies could be useful in the interpretation of a positive cross-match, since IgG antibodies are damaging to the graft whereas IgM antibodies are not.