Accommodation in ABO‐incompatible organ transplants

Abstract

Accommodation refers to a condition in which a transplant (or any tissue) appears to resist immune-mediated injury and loss of function. Accommodation was discovered and has been explored most thoroughly in ABO-incompatible kidney transplantation. In this setting, kidney transplants bearing blood group A or B antigens often are found to function normally in recipients who lack and hence produce antibodies directed against the corresponding antigens. Whether accommodation is owed to changes in anti-blood group antibodies, changes in antigen or a change in the response of the transplant to antibody binding are critically reviewed and a new working model that allows for the kinetics of development of accommodation is put forth. Regardless of how accommodation develops, observations on the fate of ABO-incompatible transplants offer lessons applicable more broadly in transplantation and in other fields.

Toward a solution for cardiac failure in the newborn

“…Monomeric antigen released by the transplant or soluble saccharides released by gut might thus cause anergy or deletion whereas release of membrane fragments with clustered antigen might stimulate responses (61). This process also potentially facilitates development of accommodation and other phenomena, explaining the occurrence of accommodation and tolerance in sequence sometimes seen in experimental systems (62). …”

“…Work by one of us (LJW) indicates these antibodies might recognize determinants not present in the graft and hence are not subject to the processes that engender tolerance (69). On the other hand, as we discuss in detail elsewhere (62, 71, 72), absence of antibodies in serum against donor antigens, particularly blood group antigens cannot be taken as proof of tolerance because organ transplants can absorb enormous amount of antibody when accommodation is present. To the extent such absorption occurs, donor-specific antibodies, against blood group antigens or HLA, might be detected after graft injury compromises the ability of a graft to process bound antibodies (62, 71).…”

“…Since B cells specific for saccharide antigens turnover continuously, it is not clear why older recipients of ABO-incompatible grafts do not also eventually develop tolerance to allogeneic saccharides in their grafts (60). Various testable explanations might be proposed (61, 62). …”

“…One of the important clinical advances in transplantation in the newborn was the discovery that for overall outcome, one can ignore ABO-compatibility (79). Even in mature individuals who make natural antibodies, incompatibility of saccharide antigens has little or no impact on outcome (62). But, there is some evidence that development of tolerance to incompatible blood group antigens in a cardiac transplant might limit responses to MHC (T cell dependent antigens) antigens (68).…”

Xenotransplantation literature update, May/June 2018

“…Mattos et al. have written a review of the ABO‐incompatible transplantation studies with a focus on the observation that grafts that express A or B antigens function normally in recipients that have a measurable antibody response to those antigens . Termed accommodation, the authors suggest a new paradigm for how this happens and chart a new path forward for addressing these issues in xenotransplantation as well as other fields.…”