Antibody-mediated Transplant Rejection Research Articles

Autoantibodies—epiphenomena or biological clues

The potential roles for autoantibodies in renal transplantation are increasing, as illustrated by a recent report of polyreactive autoantibodies produced by B-cell clones from a kidney transplant recipient that can bind apoptotic cells and activate complement. Such autoantibodies have the potential to amplify microcirculation injury caused by alloantibody in antibody-mediated transplant rejection.

675 CD19 Monitoring after Rituxamab in Patients with Cardiac Transplant Antibody Mediated Rejection (AMR)

675 CD19 Monitoring after Rituxamab in Patients with Cardiac Transplant Antibody Mediated Rejection (AMR)

516 Seasonal Variations in Cardiac Transplant Antibody-Mediated Rejection

516 Seasonal Variations in Cardiac Transplant Antibody-Mediated Rejection

ABO Incompatible Kidney Transplantation—Current Status and Uncertainties

In the past, ABO blood group incompatibility was considered an absolute contraindication for kidney transplantation. Progress in defined desensitization practice and immunologic understanding has allowed increasingly successful ABO incompatible transplantation during recent years. This paper focused on the history, disserted outcomes, desensitization modalities and protocols, posttransplant immunologic surveillance, and antibody-mediated rejection in transplantation with an ABO incompatible kidney allograft. The mechanism underlying accommodation and antibody-mediated injury was also described.

A complementary approach to treating antibody-mediated transplant rejection

Current treatment for antibody-mediated kidney transplant rejection is inadequate. Tillou and colleagues administered recombinant C1 inhibitor to block complement activation to prevent antibody-initiated injury in sensitized baboon recipients of kidney allografts. These early but encouraging results support further testing of the safety and efficacy of complement inhibition as part of a comprehensive strategy to treat this disease, both in animal models and ultimately in humans.

Prevention trumps treatment of antibody-mediated transplant rejection

Belying the spectacular success of solid organ transplantation and improvements in immunosuppressive therapy is the reality that long-term graft survival rates remain relatively unchanged, in large part due to chronic and insidious alloantibody-mediated graft injury. Half of heart transplant recipients develop chronic rejection within 10 years - a daunting statistic, particularly for young patients expecting to achieve longevity by enduring the rigors of a transplant. The current immunosuppressive pharmacopeia is relatively ineffective in preventing late alloantibody-associated chronic rejection. In this issue of the JCI, Kelishadi et al. report that preemptive deletion of B cells prior to heart transplantation in cynomolgus monkeys, in addition to conventional posttransplant immunosuppressive therapy with cyclosporine, markedly attenuated not only acute graft rejection but also alloantibody elaboration and chronic graft rejection. The success of this preemptive strike implies a central role for B cells in graft rejection, and this approach may help to delay or prevent chronic rejection after solid organ transplantation.

Human Leukocyte Antigen Class I Epitopes: Update to 103 Total Epitopes, Including the C Locus

Epitopes of human leukocyte antigen (HLA) are the sites to which the antibodies bind. We identify here 103 HLA class I epitopes shared by groups of class I antigens. In particular, our emphasis was on identifying epitopes exclusive to the C-locus antigens or interlocus epitopes among A, B, and C antigens. The use of monoclonal antibodies or alloantibodies eluted from HLA recombinant single antigen cell lines tested with a panel of single antigen beads have proved very useful in the identification of the epitopes. Alloantibodies absorbed onto then eluted from HLA single antigen cell lines and monoclonal antibodies were tested with a panel of 95 A-, B-, and C- single antigen beads and the HLA specificities determined. Each epitope was defined by amino acids shared exclusively by the positive antigens for each antibody. In addition to the 58 A and B class I epitopes identified in an earlier study, we add 45 more new A, B, C epitopes including, for the first time, epitopes found on C locus antigens. Beads bearing single antigens tested with monoclonal or eluted alloantibodies proved very powerful in identifying epitopes shared among HLA antigens. These epitopes are the targets of the antibodies. Antibody specificities to non-donor-specific antigens, often found in sera of transplant patients, can now be understood as reactions to epitopes shared with the donor specific antigens. The importance of identifying these epitopes is that they may be the "transplantation antigens" responsible for antibody-mediated transplant rejection.

The use of apheresis in immune renal disorders.

Rapidly progressive glomerulonephritis (RPGN) is often associated with the presence of autoantibodies. Included in this group are the glomerulonephritides associated with anti-GBM antibody (Goodpasture's syndrome). IgA mesangial deposition (the renal component of Henoch-Schönlein purpura), lupus erythematosus, cryoglobulinemia and the antineutrophil cytoplasmic antibody (ANCA)-associated pauci-immune group. In each of these cases, apheresis may provide a therapeutically useful option. Apheresis has also been found useful in certain types of antibody-mediated transplant rejection and in lowering the levels of preformed cytotoxic antibodies which may preclude transplantation. Finally, there are renal diseases in which the immune component is less clearly involved with pathogenesis but for which apheresis may offer a clear benefit, such as in the renal failure associated with 'cast nephropathy' (multiple myeloma) or the recurrence of FSGS (focal segmental glomerulosclerosis) in transplanted kidneys. It is the purpose of this paper to review the evidence supporting the use of apheresis in immune-related diseases.