Transplantation Laboratory – Manchester Royal Infirmary

Transplantation Laboratory – Manchester Royal Infirmary

In the continuing series of articles about the work behind our visits to clinic I was interested to find out more about the work of the Transplantation Laboratory at Manchester Royal Infirmary (MRI) and recently met Amanda Robson Clinical Scientist who kindly took time to talk about its work.

The Transplantation Laboratory covers three key areas of work.

  • Solid organ Transplantation
  • Stem Cell Transplantation
  • Research & Innovation

It would be too much to try and capture in just one article. Therefore I’ll cover the different aspects of its work in future articles. In this article we cover Solid Organ Transplantation.

I have tried to keep it simple but it’s a complex subject so I hope it’s not too difficult to understand.

Firstly on Overview

The Transplantation Laboratory is a regional pathology service and as such offers a wide range of high quality services using state of the art technologies. The main services provided by the Transplantation Laboratory are as follows:

  1. a) Solid organ transplantation – The laboratory provide supports for

Kidney, kidney and pancreas, pancreas and islet cell transplantation programmes at MRI

Cardiothoracic organ transplantation at Wythenshawe hospital

Corneal transplantation at the Manchester Royal Eye Hospital, Victoria hospital Blackpool and North Manchester Hospitals

  1. b) Haemopoietic Stem Cell Transplantation – the Laboratory provides support for the haemopoietic stem cell transplantation programmes at Central Manchester Foundation Trust (MRI and RMCH). The laboratory provides molecular typing of patients and their potential donors who may need a stem cell or bone marrow transplant.
  2. c) Research and Innovation – the Transplantation Laboratory participates in innovative research and innovation relevant to the clinical services provided to ensure that MRI continually improve their service provision in line with clinical evidence base.

The Laboratory is part of a network which is cross-directorate and is known as the Manchester Institute of Nephrology and Transplantation (MINT). MINT’s aim is to improve and develop the research and educational activities of nephrology, dialysis and transplantation service to achieve the best possible care for transplant patients.

Geographical areas

  • Kidney transplantation – covers from Barrow down to Crewe in the North West (excluding Merseyside).
  • Stem cell transplantation – MRI including the children hospital, Blackpool and Liverpool Children’s hospital.
  • Pancreas transplantation – covers east of the Pennines including all of west Yorkshire.
  • Heart and Lung Transplantation – covers all of the North West including North Wales and Merseyside.

The Laboratory employs about 50 staff across all areas of its work. They range from Clinical Scientists who require a 1st degree and 3 years specialist training and ongoing professional training, laboratory staff who require GCSE standards to enter the work and technical staff who require a degree to enter the work. Staff within the laboratory is split into three teams.

  • Multi-discipline team who carry out work on solid organ transplantation and antibody testing.
  • Bone marrow and stem cell staff. Different levels of staff carry out this work.
  • Laboratory team who carry out and label test results.

However people are rotated around the teams on a regular basis to transfer skills and knowledge.

National Training

The University of Manchester provides a Masters course for students studying to be Clinical Scientist and the Laboratory works in partnership with them to provide the location for the practical element of the course.

Transplantation – an overview

When organs are donated a blood sample is sent to the Laboratory for HLA-typing. The HLA type is compared to a national database of all those patients waiting on the transplant list held at Bristol.

When a recipient has been identified, a sample of donor cells is sent to the Transplant Laboratory in the recipient’s hospital. The donor cells are mixed with a sample of the recipient’s blood which may or may not contain antibodies in a procedure called crossmatching.

This same procedure is used when someone wishes to be a Living Donor.

There are three key strategies in the process for solid organ transplantation –

  • HLA tissue typing
  • HLA antibody testing
  • Profiling and cross matching

Human leukocyte antigen (HLA) Tissue typing (Antigens are foreign substance which induces an immune response in the body, especially the production of antibodies)

The HLA’s in our bodies are unique to that individual and HLA’s refers to a group of markers on the surface of a cell that the individual’s immune system recognises.  The immune system can spot the difference between self and non-self HLA’s in our bodies. If it’s a non-self-marker the body will try to reject it as it’s seen as a “foreign body”.

HLA Tissue typing means a series of DNA based laboratory tests whereby an individual’s HLA genes are characterised and the “markers” on the cells identified.  These tests are performed twice prior to transplantation and it’s important to minimise the number of HLA mismatches between donor and recipient “markers” to reduce the risk of rejection. The best transplant outcome happens when a patient’s HLA and the donor’s HLA closely match.

HLA specific antibody testing – individuals can produce antibodies which can happen following exposure to non-self HLA during pregnancy, blood transfusion or transplantation. These antibodies are detected in serum and can potentially react with a donor organ and cause transplant rejection.  It’s important that patients awaiting transplantation are screened for the presence of antibodies. Samples for antibody screening are sent to the laboratory on a monthly basis from patients on the transplant list. When a patient is known to have antibodies against a particular HLA then that HLA type would not be permissible in a donor for that patient.

Crossmatching – is used to determine compatibility between a donor and recipient in organ transplantation.

Crossmatching is a pre-transplant test in which donor lymphocytes (one of the subtypes of white blood cell in a vertebrate’s immune system) are tested against serum samples from the potential recipients to ascertain whether any donor reactive antibodies are present that would cause transplant rejection. Antibodies that cause a positive crossmatch test are normally not wanted. That is why a negative crossmatch is required.

It is very unusual to have a positive crossmatch because of the previous tests carried out by the Laboratory. If a positive crossmatch has been identified then there is an investigation as to why because it’s so rare.

Markers

There are 6 markers that sit on the cell surface. If markers are closely matched then the body won’t recognise the donor organ. If not closely matched the body will see it as the foreign body and try to reject the donor organ. That’s why you might hear the terms 1or 2 or 3 or 4 or 5 or 6 out of 6 match.

Immunological Camouflage If it’s a good match the body doesn’t easily recognise, or find,  the donor organ because it’s better “camouflaged” and generally speaking the recipient won’t need as many anti-rejection drugs as the body doesn’t see the donor organ because the markers are hidden on the cell surface and so the recipients body is more happy to accept the donated organ.

Virtual crossmatch 

A “virtual crossmatch” can be performed pre-transplant for selected patients whereby the donor HLA type is reviewed against a patient’s antibody profile to determine whether the patient has donor-directed antibodies that would cause a positive crossmatch result. The purpose of this process is to reduce cold ischaemia (insufficient supply of blood to the retrieved kidney) time without compromising the safety of the transplantation.

Time scale for donor crossmatching

1 Notified of local donor by Transplant co-ordinator – 1 hour

2 Blood sample sent to Transplantation Laboratory – 5 hours

3 HLA type of donor available – matching programme run,  liaise with UK Transplantation (in Bristol) for short list of patients 1-2 hours

5 Performs crossmatch 4-5 hours

Conclusion

It’s a complex process and an awful lot of work is done behind the scenes to ensure the best possible match from donor organ to recipient. That’s why we give all the blood samples when we go to clinic either before a transplant, during the transplant work process or post-transplant. MRI’s Laboratory holds over ?? of our blood samples ready to compare them for our overall benefit.