Projects

The Laboratory and Clinical Management of the Highly Sensitised Transplant Patient - 14^th Workshop Special Interest Group

Although renal graft and patient survival has improved remarkably over the last two decades the issue of the management of the highly sensitised patient remains a significant laboratory and clinical issue. Despite reduction in the use of blood transfusion as a therapy over this period there is still a significant proportion of patients who have a panel reactive antibody (PRA) of >50% (approximately 10-15%). Many of these are mutiparous or regraft patients. The main impact of high levels of sensitisation in these patients is an increase in the incidence of positive crossmatches, hence a delay in time to grafting, resulting in a longer waiting time on dialysis. In addition there is a group of patients who while not necessarily having a high PRA, have HLA antibodies which precludes them from a specifically targeted living related,or living unrelated transplant.

Several steps can be taken in order to fully maximise the chances of these patients receiving a graft with acceptable outcome within a reasonable time frame. Firstly from the laboratory aspect accurate and sensitive characterisation of HLA class 1 and class 2 antibodies is required in addition to sensitive and reproducible crossmatch procedures. From the clinical perspective, several strategies can be employed designed to immunomodulate the highly sensitised patient in order to reduce the PRA level and increase the chance of receiving a successful graft. These strategies include:

1) The use of intravenous immunoglobulin (IVIG) as a means of reducing PRA levels. This is thought to act mainly through the idiotype network but additional mechanisms remain as possibilities.
2) The use of plasmapheresis as a means of immediately reducing the levels of antibody. This strategy is often used in conjunction with other treatments e.g. IVIG.
3) In the living related situation donor specific transfusions administered under immunosuppressive cover have been used in attempts to reverse a patient's HLA immunisation status.

Immunosuppressive drugs are used in combination with these therapies at different time points in an effort to maximise the desired immunomodulatory effects. There are numerous reports in the literature using these and other therapies in different combinations at different dosages and at different time intervals. All of these strategies require the continuous involvement of HLA laboratories in monitoring the effectiveness of these treatments.

The principal aim of this special interest group therefore is to gather as much information as possible on the different strategies used in transplant units and to draw some conclusions regarding the optimal approach. Many strategies have proved ineffective and unfortunately have not always appeared in the literature, but nevertheless are important to document and may assist in maximising strategies.

Similar issues confront clinicians responsible for the care of cardiac, lung and liver transplant patients. As with renal patients we wish to collate information on the effectiveness of different immunomodulatory approaches in these situations. While there are many shared issues there are obviously other issues which are organ specific. If you have experience in these areas and wish to share and discuss yours and other participant's data please contact us on either of the e-mail addresses shown below. We would also be interested in hearing from anyone who would like to be part of a steering group responsible for documenting in more detail the issues to be addressed and the form of the data to be collected.An electronic newsletter will be prepared to keep all participants informed.

April, 2005, Update

Sera from highly sensitised renal transplant recipients are about to be circulated to several laboratories for antibody identification by several techniques with a range of sensitivities i.e CDC, ELISA, Luminex. The sera derive from sequential blood samples taken from renal patients who have undergone antibody ablation therapy and then subsequently transplantation. These samples have been provided by Andrea Zachary from the John Hopkins University in Baltimore. Results obtained using the various techniques will be presented and discussed at the meeting in Melbourne. In addition to providing useful comparative results on different techniques, the issue of inter-laboratory variation can be addressed as well as the clinical significance in the ablation context, of low level antibodies only detected by techniques with a high degree of sensitivity.

This workshop project will be presented as part of the programme on the second day of the workshop .This day is entitled “Pre-sensitization and matching in solid organ transplantation –optimal approaches diagnosis and therapy” One session on this day will be devoted to “pre-transplant monitoring and antibody ablation protocols in the highly sensitized patient” We are assembling an impressive list of participants for this meeting including Robert Montgomery and Andrea Zachary.

We hope at the end of the meeting to be able to agree to some recommendations on clinical and laboratory aspects of de-sensitization which can be used by units establishing protocols.

Project Co-ordinators:

Solomon Cohney
Renal Transplant Unit
The Royal Melbourne Hospital, Parkville, Victoria, AUSTRALIA 3050
Email: Solomon.Cohney@wh.org.au

Brian Tait
Victorian Transplantation and Immunogenetic Service
The Royal Melbourne Hospital, Parkville, Victoria, AUSTRALIA 3050
Email: bdtait@arcbs.redcross.org.au

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Projects

The Laboratory and Clinical Management of the Highly Sensitised Transplant Patient - 14th Workshop Special Interest Group

April, 2005, Update

The Laboratory and Clinical Management of the Highly Sensitised Transplant Patient - 14^th Workshop Special Interest Group