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*

Abstract

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 (> or = 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 1,290 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 = 1,218) (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.

Allosensitization Does Not Increase the Risk of Xenoreactivity to ??1,3-Galactosyltransferase Gene-Knockout Miniature Swine in Patients on Transplantation Waiting Lists

“…Cytotoxicity mediated by antinon-Gal IgG antibodies, however, was found in only two out of 29 human sera tested. While the potential role of anti- donor IgM antibodies in xenotransplantation remains to be determined, the presence of pretransplant, donor-specific IgM antibodies has no correlation with short-term and longterm renal graft outcome in allotransplantation (26). In fact, renal allotransplantation in spite of high levels of pretransplant IgM has been performed successfully in the context of ABO incompatibility using a strategy of partial IgM depletion and an immunosuppressive regimen aimed at inducing a state of accommodation (27,28), although accommodation has yet to be observed in a large animal xenograft model.…”

The role of complement in antibody-mediated rejection in kidney transplantation

“…53,54 Limitations of this approach are that the ability of DSAs to bind to complement factors varies and that many other factors might affect complement activation in vivo. For example, IgM activates complement pathways, but a positive crossmatch due to IgM has historically been considered to have little effect on renal transplant outcomes, 55,56 or may even be protective. 57,58 Conversely, other studies have suggested that IgM might cause antibody-mediated graft damage.…”

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

“…A fairly widespread belief exists that antibodies of the IgM type detected during crossmatching are often autoantibodies, are harmless, and should not be considered for transplantation [9]. It has also been claimed that IgM antibodies may be beneficial [10].…”