XM-ONE® Multicenter study

XM-ONE® endothelial cell crossmatch was evaluated in a multicenter study in kidney transplantation designed to detect AECA associated with allograft rejection (Breimer, M, Rydberg, L, Jackson, AM et al, Transplantation 2009, 87(4):549-556). The multicenter study shows that XM-ONE® contributes valuable information in transplantation diagnostics.

The main objectives of the international multicenter study were to determine the frequency of XM-ONE® positive patients in the transplanted population and investigate the difference in occurrence of rejection episodes after transplantation between patients with a positive and a negative XM-ONE® result.

Patient enrollment was based on acceptance for transplantation as determined by conventional cytotoxic and/or flow cytometry based lymphocyte crossmatch results. A total of 147 patients were evaluated in six transplant centres, both in the US and in Sweden.

XM-ONE® positive patients experienced MORE early rejections.

A number of publications have highlighted the importance of antibodies against endothelial cells and its association to rejections and graft loss. In the study 24% (35/147) of the patients had a positive XM-ONE® test result. These patients had a significantly higher risk for rejection episodes than those negative with XM-ONE®. All acute rejections in the XM-ONE® positive patients occurred within the first three weeks of the study (46%, 16/35) while the XM-ONE negative patients had a lower incidence of rejections and only 5% of the rejections occurred within the first three weeks (total 12%, 13/112 entire study period).

XM-ONE® positive patients developed more severe types of rejections.

Six of seven C4d positive biopsies were found in the XM-ONE® positive group. Only one graft loss occurred in the study and this patient had a positive XM-ONE® test.

Sustained increase in serum creatinine levels

Serum creatinine is the most commonly used indicator of renal function. An early sustained increase in serum creatinine is a known risk factor for graft loss in kidney transplant patients. XM-ONE® positive patients in the multicenter study had significantly higher levels of serum creatinine at 3 (p<0.05) as well as 6 months (p<0.05) after the transplantation.

XM-ONE® positive patients experience rejections also in the absence of donor specific HLA antibodies

In the study 113 patients had flow cytometry LXM in addition to CDC. Among patients being XM-ONE positive and Flow LXM negative 42% of the patients had a rejection episode. 14 patients were positive in Flow LXM but still considered safe for transplantation. None of these patients being positive in Flow LXM and negative in XM-ONE experienced a rejection (0/7 patients). Of those being positive in both XM-ONE and in Flow LXM 4/7 patients (57%) had an early rejection episode (27).

Conclusion

The study showed that the XM-ONE® test can detect an antibody population not possible to detect with lymphocyte crossmatch tests that is strongly associated with rejection episodes and reduced kidney function after transplantation. Thus the XM-ONE® test can identify patients at risk of antibody-mediated rejections.