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