We describe two cases of hyperacute humoral rejection of living related kidney grafts despite negative pretransplantation T- and B-lymphocyte flow cytometric crossmatches and blood group identity. Retrospectively, antiendothelial IgG antibodies were detected on a panel of umbilical cord cells in the first case, and IgM antibodies against donor endothelial precursor cells were detected using a new endothelial cell crossmatch kit in the second case. Standard crossmatch methods using donor lymphocytes failed to detect these pathogenic antibodies and did not predict the danger of hyperacute rejection.
[Show abstract][Hide abstract] ABSTRACT: Antibody-mediated rejection (AMR) is a unique, significant, and often severe form of allograft rejection that is not amenable to treatment with standard immunosuppressive medications. Significant advances have occurred in our ability to predict patients at risk for, and to diagnose, AMR. These advances include the development of newer anti-human leukocyte antigen (HLA)-antibody detection techniques and assays for non-HLA antibodies associated with AMR. The pathophysiology of AMR suggests a prime role for antibodies, B cells and plasma cells, but other effector molecules, especially the complement system, point to potential targets that could modify the AMR process. An emerging and potentially larger problem is the development of chronic AMR (CAMR) resulting from de novo donor-specific anti-HLA antibodies (DSA) that emerge more than 100 days posttransplantation. Therapeutic options include: (1) High-dose intravenously administered immunoglobulin (IVIG), which has many potential benefits. (2) The use of IVIG+rituximab (anti-CD20, anti-B cell). (3) The combination of plasmapheresis (PP)+low-dose IVIG with or without rituximab. Data support the efficacy of all of the above approaches. Newer approaches to treating AMR include using the proteosome inhibitor (bortezomib), which induces apoptosis in plasma cells, and eculizumab (anti-C5, anticomplement monoclonal antibody).
[Show abstract][Hide abstract] ABSTRACT: Anti-endothelial cell antibodies (AECAs) are thought to be involved in the development of renal allograft rejection. To explore this further, we determine whether AECAs play a role both in predicting the incidence of allograft rejection and long-term outcomes by analysis of serum samples from 226 renal allograft recipients for AECAs pre- and post-transplant. Surprisingly, the presence of pre-existing AECAs was not associated with either an increased risk of rejection or a detrimental impact on recipient/graft survival. Subsequent de novo AECAs, however, were associated with a significantly increased risk of early acute rejection. Moreover, these rejections tended to be more severe with a significantly increased incidence of both steroid-resistant and multiple episodes of acute rejection. The acute rejections associated with de novo AECAs did not correlate with C4d deposition at the time of renal biopsy, but did demonstrate an association with the presence of glomerulitis and peritubular capillary inflammation. Significantly more patients with de novo AECAs developed graft dysfunction. Thus, our prospective study suggests the emergence of de novo AECAs is associated with transplant rejection that may lead to allograft dysfunction.
Kidney International 10/2010; 79(6):655-62. DOI:10.1038/ki.2010.437 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe Acute Hepatitis is a disease that causes rapid development of liver failure with coagulopathy and encephalopathy. Due to the irreversibility of this condition, the majority of cases should be treated with liver transplantation. However, it is difficult to obtain liver grafts due to the shortage of cadaveric donors and the need for urgent transplantation. An innovative therapy is being used in these cases: Auxiliary Partial Orthotopic Liver Transplantation. This technique consists of resection of the part affected of the liver and to transplant a partial graft allowing the original liver to recovery and a gradual withdrawal of immunosuppression. Material and Methods: A literature review of articles in the Medline-mesh platform with the terms “fulminant hepatitis”, “acute liver failure”, “liver transplantation” and “auxiliary partial orthotopic liver transplantation” plus governmental and official sites to obtain data of epidemiological studies. Results:
This technique was recently described with good patient survival rates and it has not been performed in Brazil. Among the advantages are the suspension of immunosuppressive therapy due to the recovery of the original liver and reducing its side effects, and also posing the option of using grafts from living donors. Conclusion: Auxiliary Partial Orthotopic Liver Transplantation is a feasible treatment as shown in international transplant centers. It must be done by properly trained and skilled teams and it will represent an evolution in the liver transplantation in Brazil.
Achim Lother, David Fürst, Stella Bergemann, Ralf Gilsbach, Florian Grahammer, Tobias B Huber, Ingo Hilgendorf, Christoph Bode, Martin Moser, Lutz Hein
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