Anti-donor antibody class switching after liver transplantation

The humoral immune response directed against donor antigens was monitored by flow cytometry in 17 liver transplant patients using donor leukocytes as targets. Overall, donor-specific antibodies developed in 15 patients; these included all 9 patients who had experienced a biopsy-proven episode of acute rejection and 6 out of 8 patients who had not had an acute episode of rejection. The isotypes of the donor-specific antibodies in the 9 patients who had experienced an early episode of acute rejection were IgG in 8 patients, IgE in 8 patients, and IgA in 6 patients; all 9 patients had IgE and/or IgA antibodies. In the 6 patients who showed no evidence of acute clinical rejection but nevertheless developed donor-specific antibodies, the isotype was IgM associated in 5 of them, with an immunoglobulin class switching to the IgG isotype; none of these patients had antibodies of the IgA or IgE isotype. These results indicate that the lack of rejection of a liver allograft does not necessarily result from a lack of immune response against donor antigens. Rather, the distinct pattern of (cytokine dependent) immunoglobulin class switching suggests that the lack of liver graft rejection may be the result of an immune activation pathway distinct from that resulting in graft rejection.