Clinical importance of non-HLA antibodies in solid organ transplantation

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Purpose of review

The clinical importance of HLA-specific antibodies for organ allograft outcome is well established. Antibody-mediated rejections of HLA-identical kidney transplants and rejections in the absence of detectable HLA antibodies, however, indicate that non-HLA antibodies also play a significant role.

Recent findings

Non-HLA antigens, such as the polymorphic major histocompatibility complex class I-related chain A, expressed on endothelial cells, have been implicated in the pathogenesis of hyperacute, acute, and chronic organ allograft rejections. The use of donor endothelial cells as targets in pretransplant and posttransplant cross-matches will facilitate detection and specificity determination of other clinically relevant non-HLA antibodies. Non-swine leukocyte antigen–antibody responses are also receiving increasing interest as important mediators of acute vascular rejection of porcine organ xenografts; acute vascular rejection is the next big hurdle preventing clinical xenotransplantation.


Non-HLA antibody responses are receiving increasing interest in acute and chronic rejection, and specificity, affinity, and pathogenicity need to be investigated to estimate their contribution. This review summarizes past and current knowledge of the clinical importance and specificities of non-HLA antibodies and mechanisms by which these antibodies may contribute to graft destruction in organ allotransplant and xenotransplant recipients.

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