Ladies and gentlemen,
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“A complete understanding of non-HLA antibodies, particularly those that attack the endothelial cells in vessels surrounding a graft, is essential to maximize the impact of available immunosuppression strategies”, Professor. Kathryn Wood, Oxford, UK, told at the Monday morning symposium at The Transplantation Society’s 13th international congress in Vancouver, Canada.
This AbSorber sponsored symposium was focusing on improving the outcome in kidney transplantation by enhanced risk assessment and was chaired by Professor Ron Shapiro, Pittsburgh, PA. Though the early morning, more than 300 participants had gathered for the meeting.
Predictors of graft failure in kidney transplantation
Professor Josep Grinyo from Bellvitges Hospital, Barcelona, Spain, started the symposium by stating that, although graft survival has dramatically improved in kidney transplantation, patients experiencing acute rejections still have a poor outcome. Among the risk factors for acute rejection Prof Grinyo especially pointed out HLA mismatches, cellular response/”sensitization”, and humoral responses, depending either on HLA or non-HLA antibodies.
The more tools we have the more complex it gets
Professor Kathryn Wood was the next speaker and continued with the message that “transplant specialists have always tried to bring new tools into our armamentarium to assess risk between individual donors and recipients”. She presented data from retrospective studies that pre-assessment of new transplant patients can enhance the current standard of risk assessment. “The more tools we have, the more complex it gets, but understanding how to best use the immunosuppression we have available for each patient will have a huge impact on outcomes, particularly long-term outcomes,” said Prof. Wood. Although clinical teams test for HLA antibody reactivity before a transplant, Prof. Wood said antibody-mediated rejection (AMR) still shows up in a subset of recipients with negative crossmatches.
Non-HLA AECA is clinically relevant
Prof Wood continued by stating that anti-endothelial cell antibodies are clinically relevant for the transplant outcome. Irreversible vascular rejections can occur in HLA identical sibling transplants and also in the absence of anti-HLA- antibodies. Furthermore, AECA are present before transplantation and they can also be eluded from rejected grafts. Based on available literature, a conservative estimate would place graft loss due to preexisting non-HLA antibodies at 3% of patients per year. A combination of clinical criteria and laboratory analysis can be used to diagnose AMR. Using detection tools that have only recently become available, researchers have identified a variety of specific targets for non-HLA antibodies, and “there’s an array of molecules that can trigger an antibody response” leading toward graft rejection.
Testing for non-HLA antibodies, a clinical approach
Dr Anat Tambur, Director of the Transplant Immunology Laboratory at Northwestern University Hospital in Chicago, IL, reported from an ongoing study with XM-ONE at Northwestern. In a pilot study of patients on their waiting list Dr Tambur showed that about 20% of the patients had a positive XM-ONE test, i.e. where tested positive for non-HLA antibodies, although they were negative both for HLA and MIC A antibodies. Furthermore, the study showed that these antibodies where polymorphic by testing one donor against a number of recipients showing donor specificity of the test. The pilot study did not show any correlation to disease or prior sensitization events.
The initial pilot study created the idea of a single center study at Northwestern University targeting approximately 200 LD transplant patients. Until today, inclusion and baseline data are available for 73 patients. Dr Tambur stated that it is still too early to draw any clinical conclusions, but presented some early data. So far data shows that two out of three patients which has elevated S-creatinine (>2g/dl) at three months post transplantation were XM-ONE positive prior to transplantation, without any presence of DSA HLA antibodies. The study is ongoing and patients are recruited during 2010. Data from the study will be available next year.
Earlier and more severe rejections in patients being XM-ONE® positive
Prof Shapiro summarized the symposium and concluded by using data from the XM-ONE multicenter study published last year in Transplantation (Breimer et al). In the study it was found that patients being XM-ONE positive (46%) had significantly more rejections than patients having a negative XM-ONE test (5%) 3 weeks after transplantation. The rejections also occurred earlier in XM-ONE positive patients and where characterized as more severe, resulting in an increased S-creatinine over time.
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