transplant immunology – a user’s guide!! dr mary keogan consultant clinical immunologist &...
TRANSCRIPT
Transplant Immunology –A User’s Guide!!
Dr Mary KeoganConsultant Clinical Immunologist & Medical
Director, NHISSOTBeaumont Hospital
Overview
A little bit about the immune system What happens in the lab when you are
listed. What happens on the night when there is
a donor. What happens when you have a living
donor What can be done for people who are
highly sensitised.
The immune system fights infection
•Distinguishes self from non-self•Attacks non-self
A transplanted organ is “non-self”
•Distinguishes self from non-self•Attacks non-self
Our Immune army – 2 main platoons
B cell platoonMake antibodiesDamage organEasy to measure
T cell platoonCause most rejectionBetter controlled than B cells
by immunosuppressionHard to measure
What are antibodies?
Proteins made by cells of the immune system(B cell platoon)
Job is to fight infection
Can damage graft Some types more
damaging that others
The immune system remembers
Memory T & B cells react quickly & strongly
Meds control new immune cells better
Difficult to controlmemory cells
If have antibodies likely to have memory cellsMemory cell
That’s not a dog
Remember how goodcat tastes?
OrganImmune System
Rejection
Avoid Hyperacute Minimise AMR Reduce Cellular Rejection
How does the immune system know my transplant is “non- self”?
Blood Group
Tissue Type (HLA type)
1000s of other differences
Immunologically ideal transplant
MUST be Blood Group Compatible
SHOULD be anti-HLA antibody compatible
IDEALLY, well HLA-matched
Even if “perfect HLA match”transplant is non-self
When you are listed History - transplants; pregnancy; transfusions.
Check blood group (twice) Check HLA type (1 full; 1 check)
Measure antibodies to HLA molecules Recheck every 3 months If sample not received, temporarily
suspended from list
How does my blood group affect my kidney?
Markers are on all your cells, not just blood cells
Blood group made up of markersGroup A – A markerGroup B – B markerGroup O – no A or B markerGroup AB – A & B markers
Your immune system reacts to markers you don’t have – they are “non-self”
Your TissueType
(HLA type)
More flags for your immune system
Use to say how
well matched
a donor is.
Antibodies to HLA
Your own tissue (HLA) type is self Other tissue types are non-self If exposed to other HLA types, you may make
antibodies & memory cells
Exposure – transplant; transfusion; pregnancy Sometimes infections cause anti-HLA
antibodies
Check what tissue types you have made antibodies to.
Aim to identify donor to whom you have NO antibody
Whats my Pgen? We measure antibodies when listing, after
transfusions and pregnancy. Recheck every 3 months Make a list of all your antibodies Match against database of thousands of
donors
Pgen is the percentage of Irish donors against whom you have antibodies.
Measure of how hard it is to find an antibody compatible donor for you
What does my Pgen mean?
Lower – antibodies against fewer donors Higher – more difficult to find ideal donor
We use allocation to “level the playing field”
Extra priority if Pgen >50% High priority if >94% Consider higher risk transplant if >94%
What happens when there is a deceased donor?
Blood sent to lab – Blood group & HLA type checked
Run matching programme to identify patients who do not have antibodies to the donor
Prepare shortlist of potential recipients who are blood group & anti-HLA antibody compatible.
Recipient short list
Clinically urgent Paediatric patients Pgen >94% Pgen > 50% Best HLA matched Recipients with rare types Longest waiting
Crossmatch Potential Recipients & back-ups
Test up to 4 potential recipients to prevent delays
Once crossmatch cleared, recipients are contacted.
If unwell, back-up patient called
If crossmatch positive due to anti-HLA transplant is increased risk, or may be too high risk to proceed.
Crossmatch measures antibody binding to donor cells
Thousands of Different cell surface proteins Positive result if antibodies to any of themOnly relevant if anti-HLA antibodies
Living Donors – Immunological
assessment
Blood Group checked locally Determine tissue (HLA) type See if recipient has antibodies
against the donor.
Determine immunological risk
Your Tissue
Type
(Aka HLA type)
More flags for your immune system
Use to say how
well matched
a donor is.
You inherit “packages” of HLA flags from each parent
Risk assessment
Low Risk – Perfect HLA match Standard Risk – No antibodies against donor
now or in the past Slight increase in risk – weak antibodies,
negative crossmatch. Increased risk – antibodies against donor;
can mitigate with immunosuppression. Detailed discussion re alternatives
High risk – unsuitable, at least without antibody removal
LD Assessment
If Immunology unlikely to preclude transplantation, assessment proceeds.
Monitor 3 monthly samples for new antibodies against the donor
Within 3 months of expected date formal review – may include crossmatch.
Crossmatch the week before transplant
My Pgen is 100%. What about me?
Means antibodies to >99.5% of population Additional priority as Pgen >94%
Living Donor If LD incompatible – Paired kidney exchange
100% reviews – define antibodies that are less damaging. Then transplant with augmented immunosuppression.
Graft Survival
3 months 1 year 3years 5years 10 years
DSA+C1q+n=15
78 71 64 64 55
DSA+C1q-n=46
91 85 82 76 67
No sig.Abs.n=145
98 97 94 86 80
% graft survival
2012/2013 – 33 of the most complex patients transplanted
Deceased donors 9 x 100% patients 12 x AMM patients
Living donors 9 -100% patients 1 – 100%ABOi 2 - AMM patients
8 because of 100% review programme
The future………..
Transplant plans for patients with Pgens of 100%
Each member of staff “adopts” a 100% patient. Detailed review of every antibody.
Review opens windows to facilitate transplant in many patients
Consider increased risk transplants in long waiting patients with few opportunities
?desensitisation
That’s not a dog
Remember how goodcat tastes?
Organ Immune System
Don’t let your puppy immune cells turn into memory cells