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. 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 platoon Make antibodies Damage organ Easy to measure T cell platoon Cause most rejection Better controlled than B cells by immunosuppression Hard 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 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 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 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 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 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 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 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+ 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 Deceased donors Living donors 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……….. 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