Tolerance in transplantation David Berglund, MD/PhD Docent of Immunology
Disclosure • Consult for a start-up developing a monoclonal CD2 antibody for use in transplantation.
Transplant tolerance • History • Present knowledge • Future directions • The treatment of today is not good enough.
How good are the results?
The clinical problem
Lack of improvement long-term
Effective at preventing acute rejection Cancer Infections Diabetes… Tacrolimus Mycophenolate Corticosteroids
Transplant tolerance – what is it? • Stable graft function in the absence of immuno- suppressive drugs, with no clinically significant detrimental immune responses or immune deficits. • “Accept the transplant as self.”
History >3,000 citations
Tolerance to foreign tissues – chimerism
Natures own experiment – pregnancy Vascular anastomosis
Mechanisms • “There are three fundamental principles for the induction of durable transplant tolerance:”
Unfortunately,… • … we don’t know any of them. • How to search for mechanisms? Central vs peripheral tolerance
Looking for mechanisms – collecting rare patients • 31-year old man with uremia • Received kidney transplant from live donor • Uncomplicated postoperative course • Basiliximab-induction, CyA, corticosteroids • Google • Vacation
Collecting rare patients First year after tx
Collecting rare patients The last 11 years First year after tx ?
Exceedingly rare (hard to find)
What have we learned? >1,000 citations
Looking through a small keyhole
Substantial heterogeneity
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