IgM antibodies identified by a DTT-ameliorated positive crossmatch do not influence renal graft outcome but the strength of the IgM lymphocytotoxicity is associated with DR phenotype*†

A positive crossmatch that is rendered negative by treating the serum with the IgM-reducing agent dithiothreitol (DTT) is generally reported not to influence short-term renal graft outcome. Its effect on long-term (3 years) cadaveric and live-donor transplant function, however, is less clear. We evaluated the effect of IgM antibodies in a DTT-ameliorated positive crossmatch (DTT-APXM) on long-term renal graft outcome in 1290 consecutive cadaveric renal transplants (8-year survival) and 384 live-donor renal transplants (7-year survival) from patients transplanted between 1990 and 1999. The data show that 1- and 8-year graft survival for cadaveric renal transplants in patients with IgM antibodies (n=72) (DWFG censored=91% and 65%; DWFG not censored=90% and 60%) was not significantly different from the group without IgM antibodies (n=1218) (DWFG censored=92% and 71%; DWFG not censored=87% and 55%) (log-rank=0.25 for DWFG censored, log-rank=0.92 for DWFG not censored). The one- and seven-year graft survival for live-donor renal transplants in patients with IgM antibodies seen in a DTT-APXM (n=22) (DWFG censored=95% and 83%; DWFG not censored=95% and 66%) was not significantly different from the group without IgM antibodies (n=362) (DWFG censored=94% and 81%; DWFG not censored=92% and 73%) (log-rank=0.61 for DWFG censored, log-rank=0.89 for DWFG not censored). DR phenotype was found to be associated with the strong (>40% cell death) IgM reactivity in both black and white patients. In white patients, DR2 was more frequently seen with a strong IgM crossmatch (48.2%) than in molecularly typed controls (28.5%) (P<0.03) and concomitant with that DR increase, DR4 was decreased in white patients (6.8%) compared with controls (25.5%) (P<0.02). In black patients with strong IgM reactivity, DR6 was increased in patients (46.1%) compared with controls (20.5%) (P=0.07) and concomitant with that DR6 increase, DR5 was decreased in frequency in black patients (7.6%) compared with controls (41%) (P<0.03). These data show that long-term graft survival in renal transplantation is not negatively influenced by the presence of donor-reactive lymphocytotoxic antibodies in the crossmatch ameliorated by serum DTT treatment. They also suggest that the strength of the IgM antibody response is regulated in part by certain gene (s) of the DR region.