Conversion of IgG-mediated complement-dependent cytotoxicity by reducing reagents.

Reducing reagents used in complement-dependent crossmatches reduce IgM but not IgG. A positive IgM crossmatch is not an absolute contraindication to allografting. We have studied an alloantiserum from a patient with 100% panel reactive antibody awaiting heart transplantation whose serum was reduced. Absorption of this serum with the patient's erythrocytes or leukocytes had no effect on the third-party cytotoxicity. Absorption with third-party plasma or serum was without effect. Crossmatch of this serum with an HLA-A,B,C-identical nonrelated target was positive, whereas crossmatches with the patient's HLA-identical siblings were negative. Crossmatches with the patient's five children showed one strong, three intermediate, and one weak cytotoxic reactions. No antibody-dependent cellular cytotoxicity activity was observed. Fluorescence-activated cell sorter analyses showed no IgM but strong IgG1 antibody present before and after reduction of the serum. Our data indicate some IgG antibodies are reducible. The transplantation outcome in the presence of reducible IgG alloantibodies is not known, but it is possible these antibodies are associated with graft failures in patients observed to have positive standard crossmatches that become negative in the presence of reducing reagents.