transplant immunology – a user’s guide!!

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Transplant Immunology – A User’s Guide!! Dr Mary Keogan Consultant Clinical Immunologist & Medical Director, NHISSOT Beaumont Hospital

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Transplant Immunology – A User’s Guide!!. Dr Mary Keogan Consultant Clinical Immunologist & Medical Director, NHISSOT Beaumont 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. - PowerPoint PPT Presentation

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Page 1: Transplant Immunology – A User’s Guide!!

Transplant Immunology –A User’s Guide!!

Dr Mary KeoganConsultant Clinical Immunologist & Medical

Director, NHISSOTBeaumont Hospital

Page 2: Transplant Immunology – A User’s Guide!!

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.

Page 3: Transplant Immunology – A User’s Guide!!

The immune system fights infection

•Distinguishes self from non-self•Attacks non-self

Page 4: Transplant Immunology – A User’s Guide!!

A transplanted organ is “non-self”

•Distinguishes self from non-self•Attacks non-self

Page 5: Transplant Immunology – A User’s Guide!!

Our Immune army – 2 main platoons B cell platoon

Make antibodiesDamage organEasy to measure

T cell platoonCause most rejectionBetter controlled than B cells

by immunosuppressionHard to measure

               

 

Page 6: Transplant Immunology – A User’s Guide!!

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

Page 7: Transplant Immunology – A User’s Guide!!

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

Page 8: Transplant Immunology – A User’s Guide!!

That’s not a dog

Remember how goodcat tastes?

OrganImmune System

Page 9: Transplant Immunology – A User’s Guide!!

Rejection Avoid Hyperacute Minimise AMR Reduce Cellular Rejection

Page 10: Transplant Immunology – A User’s Guide!!

How does the immune system know my transplant is “non- self”?

Blood Group

Tissue Type (HLA type)

1000s of other differences

Page 11: Transplant Immunology – A User’s Guide!!

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

Page 12: Transplant Immunology – A User’s Guide!!

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

Page 13: Transplant Immunology – A User’s Guide!!

How does my blood group affect my kidney? Markers are on all your cells, not just

blood cells Blood group made up of markers

Group 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”

Page 14: Transplant Immunology – A User’s Guide!!
Page 15: Transplant Immunology – A User’s Guide!!

Your TissueType(HLA type)

More flags for your immune system

Use to say howwell matcheda donor is.

Page 16: Transplant Immunology – A User’s Guide!!

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

Page 17: Transplant Immunology – A User’s Guide!!

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

Page 18: Transplant Immunology – A User’s Guide!!

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%

Page 19: Transplant Immunology – A User’s Guide!!

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.

Page 20: Transplant Immunology – A User’s Guide!!

Recipient short list

Clinically urgent Paediatric patients Pgen >94% Pgen > 50% Best HLA matched Recipients with rare types Longest waiting

Page 21: Transplant Immunology – A User’s Guide!!
Page 22: Transplant Immunology – A User’s Guide!!

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.

Page 23: Transplant Immunology – A User’s Guide!!

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

Page 24: Transplant Immunology – A User’s Guide!!

Living Donors – Immunological

assessment

Blood Group checked locally Determine tissue (HLA) type See if recipient has antibodies

against the donor.

Determine immunological risk

Page 25: Transplant Immunology – A User’s Guide!!

Your TissueType(Aka HLA type)

More flags for your immune system

Use to say howwell matcheda donor is.

Page 26: Transplant Immunology – A User’s Guide!!

You inherit “packages” of HLA flags from each parent

Page 27: Transplant Immunology – A User’s Guide!!

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

Page 28: Transplant Immunology – A User’s Guide!!

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

Page 29: Transplant Immunology – A User’s Guide!!

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.

Page 30: Transplant Immunology – A User’s Guide!!

Graft Survival3 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

Page 31: Transplant Immunology – A User’s Guide!!

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

Page 32: Transplant Immunology – A User’s Guide!!

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

Page 33: Transplant Immunology – A User’s Guide!!

That’s not a dog

Remember how goodcat tastes?

Organ Immune SystemDon’t let your puppy immune cells turn into memory cells

Page 34: Transplant Immunology – A User’s Guide!!
Page 35: Transplant Immunology – A User’s Guide!!