Pathophysiological role of B cells and the therapeutic potential of anti-CD20 in chronic renal allograft rejection

接受肾移植(或“移植”)的患者中有50%将不得不在10年内重新透析。高危人群之一是那些产生抗体的人。为了帮助延长这些患者的移植物，该项目旨在准确地阐明抗体与移植物损伤的关系。大约60名来自300名移植受者的抗体阳性的患者将被确认。进一步的分析将取决于他们的移植物是否在恶化。如果是这样的话，将对血液和活组织标本进行检查，以试图确定抗体是否(以及如何)参与了恶化过程。所有这些患者都将接受治疗，以阻止他们的B淋巴细胞(制造抗体的细胞)工作，看看这是否会影响移植物恶化的速度。这种疗法在其他抗体相关的情况下效果良好，通常使用起来是安全的。少数抗体阳性的患者预计移植的移植物效果良好。将对这些患者进行研究，试图了解为什么抗体或T细胞不会损害他们的移植物。预计这项工作将有助于了解移植物丢失的机制，并应改善移植失败患者的预后。

50% of the patients who receive a kidney transplant (or ‘graft‘) will have to return dialysis within 10 years. One group at high risk are those who develop antibodies. To help prolong the grafts in these patients, this project aims to clarify precisely how antibodies are associated with graft damage. Approximately 60 patients with antibodies from within 300 transplant recipients will be identified. Further analysis will depend on whether their grafts are deteriorating. If so, blood and biopsy specimens will be examined to try and identify whether (and how) antibody is involved in the process of deterioration. All these patients will be offered treatment to stop their ‘B‘ lymphocytes (the cells that makes antibodies) from working, to see if this it affects the rate of graft deterioration. This therapy works well in other antibody-associated conditions and is generally safe to use. A small number of patients with antibodies are expected to have grafts that are working well. These patients will be studied to try and understand why antibodies or T cells do not damage their grafts. It is expected that this work will help understanding of the mechanisms of graft loss and should improve the prognosis of patients with failing transplants.