Clinical Use Of XM-ONE^® in focus at ASHI symposium.

Impacting outcomes in kidney transplantation: Non-HLA antibodies and Clinical Risk Assessment

The annual ASHI meeting was held in New Orleans, LA, and attracted specialists within the field of transplantation immunology. At the meeting AbSorber, together with their US distributor Olerup Inc., hosted a lunch symposium focusing on the clinical use of XM-ONE^®, Absorber's endothelial cross match test.

The Hopkins Experience With XM-ONE^®

Introducing the XM-ONE^® Proficiency Testing

Dr Håkan Hall, Head of Research and Development at AbSorber continued the discussion by reviewing the development of XM-ONE^® since the initial research at Karolinska Institutet, Stockholm, Sweden. This research was triggered by two young patients experiencing hyperacute rejections in absence of HLA antibodies (ref Sumitran-Karuppan, Transplant Immunology 1997; 5: 321-327,). In 2008 XM-ONE^® was cleared for the US market  by FDA and remains the only FDA cleared transplantation cross match. In Europe XM-ONE^® is CE marked including CD3 and CD19 enabling a simultaneous T-, B and EC cross match in the same tube. In the US the FDA cleared version is without CD3/CD19.

Ongoing Single Center Study looks at both deceased and living donor kidney transplants

Donna Phelan at Barnes Jewish Hospital, St Louis, MO shared data with the audience from their ongoing evaluation of XM-ONE^®. Close to 100 patients, 60 DD and 35 LD, have been enrolled in the study. Due to initial problems with controls 77 (IgG) and 89 (IgM) patients have been evaluated. Notable from the demographics was that the XM-ONE^® positive patients were less sensitized than the negative patients suggesting that the positivity was due to non-HLA antibodies. Furthermore only 13% of the XM-ONE^® positive patients had a positive T-cell cross match.

In the study a total of five grafts were lost thus far. All of these patients were XM-ONE^® positive. The study is still ongoing but so far indicate that XM-ONE^® positive pre transplantation correlates to earlier and more severe acute rejections, and increases in graft loss (5/5 graft losses were positive pre transplant). Two important questions were brought to the forefront;

• Would intervention based on positive result modify outcomes?
• How can prognostic utility be improved?

Clinical Case Reports

The symposium concluded with case reports from the different participants. A case of graft loss was presented from Barnes Jewish. The patient, who was an AB to 0 LURTx was HLA negative in both cross match and by PRA and was treated with rituximab and pheresis to remove AB antibodies and transplanted with a titer of 1:8. Shortly after transplant the patient became anuric and a biopsy showed AHR, C4d and arteritis. Isoagglutination titer was 1:4 and HLA DSA testing was negative. The graft could not be saved and nephrectomy was performed day 6 post transplantation. XM-ONE^® test was performed after the nephrectomy and showed strong IgG positivity. The patient was successfully re-transplanted prior to a negative XM-ONE^® result and standard negative cross match test.

From Johns Hopkins a case with a male kidney transplant recipient experienced three hyperacute rejections was presented. The rejections all occurred within 12 hours after transplantation and were C4d negative. Before each transplantation the patient had been tested negative for HLA antibodies against the donor but had shown endothelial cell antibodies. At the third transplantation the patient received extensive rescue therapy with plasmapheresis, rituximab, eculizimab, ATG, bortezomib and splenectomy but the kidney was not to be saved.

At Karolinska Hospital a similar case was presented, that being an AB0i kidney transplant recipient with no HLA antibodies against the donor (Ref: Holgersson, J et al, Clinical Transplants 2006). However the patient had IgM antibodies detected with XM-ONE^®. The patient was treated with rituximab, immune adsorption. Nine days after the transplantation S-creatinine started to rise and an XM-ONE^® test performed was positive but now for IgG antibodies. The T-cell cross match was negative and AB0 titers were low. Rejection therapy including immune adsorption was started and after a week the S-creatinine was normalized.

These three cases all describe patients considered to be "safe" for transplantation due to negative standard and conventional cross match tests. Occurrence of severe rejections in such patients are not uncommon and provide a challenge to the entire clinical and laboratory team. In these cases, XM-ONE^® proved to be a valuable tool in initial diagnosing the cause of the rejection/graft loss both pre- and post transplantation and also to be of value in choosing therapy and/or in allocating the organ.

Please also visit the AbSorber web site and find more references on XM-ONE and endothelial cell antibodies here.

“AbSorber is excited about the very positive interest that XM-ONE^® received at the ASHI symposium, as well as the growing interest in the transplant community around the world. It is especially encouraging to see the clinical utility of the assay being even more defined and that XM-ONE starts to assists the clinical community in decision making in organ transplantation” says, Anders Karlsson, CEO of AbSorber.

XM-ONE^® is a standardized, cell based, crossmatch test for clinical use. The use of XM-ONE^® allows you to identify patients with anti endothelial cell antibodies, a risk factor for acute rejections in organ transplantation (Holgersson, S et al, Current Opinion in Immunology 2008, 20:607–613,). XM-ONE^® provides additional information compared to the currently used lymphocyte cross match tests. For further information see package insert or visit www.absorber.se.

For information, please contact:

Marc Vegh
Front Office and Laboratory Manager

MILAN ANALYTICA AG
Baslerstrasse 15
4310 Rheinfelden/Basel
Switzerland

fon +41 (0)61 845 99 88
fax +41 (0)61 845 99 87
e-mail: marc.vegh@milananalytica.ch
www.milananalytica.ch

AbSorber AB, Box 12283, SE-122 27 Stockholm, Sweden, www.absorber.se