Role of immunoglobulin (Ig)-G and IgM antibodies against donor human leukocyte antigens in organ transplant recipients

Antibodies against HLA antigens offer a window to the response of transplant recipients to the challenge of allografts. HLA alleles produced by recombinant technology and attached to color-coded polystyrene microspheres are now in widespread use. They offer antibody detection by flow cytometry at a high level of sensitivity. Methods used in the author's laboratory for the interpretation of these tests are described. They include a correction for variable antigen density, and the binding of normal immunoglobulins to the conjugated beads. The ‘normalized ratio’ provides a good method of scoring results. Antibodies specific for the antigens of the donors were associated with kidney and heart allograft loss. Antibodies against crossreactive antigens, without reactivity against donor HLA, did not appear to increase the risk of developing chronic rejection. Antibody production by peripheral blood B cells was analyzed. The idea of sequestration of HLA antibodies in the graft as a major cause for their absence in the blood after transplantation is discussed. IgM antibodies against donor HLA antigens were found before transplantion and also were produced both early and late in the post-transplant course. In addition, IgM antibodies against donor HLA appeared to be associated with decreased survival of kidney and heart allografts.