Successful transplantation after conversion of a positive crossmatch to negative by dissociation of IGM antibody

Preliminary crossmatching usually eliminates highly sensitized patients from consideration for renal transplantation. However, if the crossmatch is positive because of the presence of IgM antibody, this activity can be eliminated by treatment with the reducing agent Dithiothreitol (DTT). Successful transplantation may then be possible in patients whose crossmatch is positive due to the presence of IgM antibody. After treatment with DTT, the sera of 25 highly sensitized patients were measured for cytotoxicity against a selected panel of 40 cells. Those whose high %PRA could be attributed to blood transfusions or previous transplants did not change with DTT. Only two patients who had developed high panel reactivity, without a clear cause, had little reactivity remaining after DTT treatment of their sera. To select patients whose crossmatch might be rendered negative by DTT treatment, we developed a “minipanel” screening protocol. Patients whose monthly PRA cells increased >30% from baseline had their serum samples treated with DTT to reduce IgM. The treated sera were tested against a panel of six cells. If there was little or no cytotoxicity, it was assumed that IgM antibody was responsible for the positive crossmatches. All subsequent cadaver donor crossmatches were done with and without DTT treated sera. Five patients (2 living-related; 3 cadaver) with current crossmatches positive before, but negative after, DTT treatment continue to have functioning kidneys 3—15 months after renal transplantation. There were no hyperacute rejections. We conclude that patients with IgM antibody can be successfully transplanted if they have a negative crossmatch after reduction of IgM antibody in their serum samples. A “minipanel” helps to identify patients who will benefit from DTT treatment.