Non-organ Specific Autoimmune Disease

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Transplant Immunology –
A User’s Guide!!
Dr Mary Keogan
Consultant Clinical Immunologist & Medical
Director, NHISSOT
Beaumont Hospital
Overview
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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
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B cell platoon
Make antibodies
Damage organ
Easy to measure
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T cell platoon
Cause most rejection
Better controlled than B cells
by immunosuppression
Hard to measure
What are antibodies?
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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
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Memory T & B cells react
quickly & strongly
Meds control new
immune cells better
Difficult to control
memory cells
Memory cell
If have antibodies likely
to have memory cells
That’s
not a dog
Remember how
good
cat tastes?
Organ
Immune System
Rejection
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Avoid Hyperacute
Minimise AMR
Reduce Cellular Rejection
How does the immune system know
my transplant is “non- self”?
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Blood Group
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Tissue Type (HLA type)
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1000s of other differences
Immunologically ideal transplant
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MUST be Blood Group Compatible
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SHOULD be anti-HLA antibody compatible
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IDEALLY, well HLA-matched
Even if “perfect HLA match”
transplant is non-self
When you are listed
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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?
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Markers are on all your cells, not just
blood cells
Blood group made up of markers
Group A – A marker
Group B – B marker
Group O – no A or B marker
Group 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
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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?
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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?
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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?
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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
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Clinically urgent
Paediatric patients
Pgen >94%
Pgen > 50%
Best HLA matched
Recipients with rare types
Longest waiting
Waiting list -
100
90
80
70
Pgen
60
50
40
30
20
10
0
0
20
40
60
80
Waiting Time (mean 24 months)
100
120
140
Crossmatch Potential Recipients &
back-ups
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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 them
Only relevant if
anti-HLA
antibodies
Living Donors –
Immunological assessment
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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
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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
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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?
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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+
C1qn=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
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Deceased donors
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Living donors
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9 x 100% patients
12 x AMM patients
9 -100% patients
1 – 100%ABOi
2 - AMM patients
8 because of 100% review programme
The future………..
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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
good
cat tastes?
Organ
Immune System
Don’t let your puppy immune cells
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