Clinically-related questions

• Why is it relevant to perform an endothelial cell crossmatch in pre-transplant evaluations?

  Despite extensive testing before renal transplantation, a large proportion of transplanted patients experience rejection. Even though negative lymphocyte crossmatch (LXM) tests indicate a lack of antibodies against HLA class I and II, many patients experience rejection episodes that might result in graft loss or decreased graft function. The clinical data in our study show a strong correlation between the presence of anti-endothelial cell antibodies and rejection episodes - despite the negative LXM.

• What correlation has been observed between lymphocyte crossmatch (LXM) and XM-ONE®?

  The majority of patients included in the study were approved for transplantation based on negative LXM. However, 14 patients were still ‘considered safe' for transplantation despite being LXM positive. Reasons for this decision included lack of donor-specific antibodies or an inconsistent LXM result. In the multi-center study, none of the patients with a positive flow LXM and a concomitant negative XM-ONE® experienced antibody-mediated rejection.

• Is there a correlation between anti-endothelial cell antibodies and long-term kidney function?

  All antibody-mediated rejections occurred in XM-ONE® positive patients. Biopsies from the first rejection episode showed that 6 patients were C4d positive. All were in the XM-ONE® positive group. Several studies have shown a strong correlation between severity of rejection episode and graft outcome.
  For mean creatinine values 3 and 6 months after transplantation, a significant difference between XM-ONE® positive and XM-ONE® negative patients was observed. Data have been published showing a strong correlation between post-transplant creatinine value and long-term graft survival.

• How specific are the anti-endothelial cell antibodies? If a patient is positive against one donor, what is the probability for also being positive against a pool?

  The probability that a patient who is positive against one individual would also be positive against a pool is relatively high, but not 100%. We have seen patients with graft losses and endothelial cell antibodies against only the donor and no reaction against other potential donors.

• Can XM-ONE® be used for crossmatch tests in deceased donors?

  Yes, as long as you can sample peripheral blood, XM-ONE® can be used. In the study, 33 of the 147 patients received kidneys from deceased donors. The result in this sub-group correlates well with the total study.

• What is the experience of auto-antibody testing with XM-ONE®?

  Although we did not include auto-antibody tests in the study protocol, a few mandatory cases were performed. In 3 patients with positive XM-ONE®, we also found auto-antibodies against endothelial cells. None of these 3 had any rejection episodes.