Immunoglobulin G subclasses and susceptibility to allosensitization in humans

Understanding the cellular basis of allosensitization is important because persistence of cytotoxic alloreactive antibodies significantly decreases the chances for receiving a second kidney graft and has a detrimental effect on graft survival rates. In this study, serum levels of IgG subclasses were compared within three groups of uremic patients with different levels of allosensitization (panel reactive antibody level > or = 70%, 10-65% and < or = 10%). All the non-sensitized patients had already lost at least one graft indicating resistance to allosensitization by the previous graft. In addition, the in vitro T-cell proliferation and immunoglobulin M and G subclass production were studied after activation by pokeweed mitogen and alloantigens. The patients' demographics were comparable. The results show that all serum IgG subclass levels in the three groups were comparable and within the range of normal control. Similarly, T-cell proliferation and the in vitro production of IgM was not significantly different. The lymphocytotoxic activity present in each IgG subclass was not associated with an increase in the respective serum subclass level or the in vitro production of the same subclass in the sensitized patients. The data indicate that humoral immunity, as reflected by subclass immunoglobulin levels, is, in fact, normal, in the three groups and that sustenance of cytotoxic antibody production reflects a specific immune response controlled by factors other than intrinsic B-cell abnormality.