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 in fluence short-term renal graft outcome. Its effect on long-term ( greater t han or equal to 3 years) cadaveric and live-donor transplant function. howe ver, is less clear. We evaluated the effect of IgM antibodies in a DTT-amel iorated 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 betwe en 1990 and 1999. The data show that 1- and 8-year graft survival for cadav eric renal transplants in patients with IgM antibodies (n = 72) (DWFG censo red = 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 ce nsored, log-rank = 0.92 for DWFG not censored). The one- and seven-year gra ft survival for live-donor renal transplants in patients with IgM antibodie s seen in a DTT-APXM (n = 22) (DWFG censored = 95% and 83%; DWFG not censor ed = 95% and 66%) was not significantly different from the group without Ig M 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 pati ents, DR2 was more frequently seen with a strong IgM crossmatch (48.2%) tha n 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 cont rols (25.5%) (P <0.02). In black patients with strong IgM reactivity, DR6 w as increased in patients (46.1%) compared with controls (20.5%) (P=0.07) an d concomitant with that DR6 increase, DR5 was decreased in frequency in bla ck patients (7.6%) compared with controls (41%) (P <0.03). These data show that long-term graft survival in renal transplantation is not negatively in fluenced by the presence of donor-reactive lymphocytotoxic antibodies in th e 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.