Transplantation Flashcards
How does graft rejection occur
T cells orchestrate the allo-immune response after transplantation and are essential for graft rejection
Mechanism: CD8 medicated cytotoxicity, CD4 mediated delayed type hypersensitive like reaction and antibody mediated injury
What are the types of organ donors
more DCD, fewer LD and DBD. Patient and allograft survival for DBD and DCD for kidney similar. Liver better rates with DBD. Donation after brain death (DBD) Donation after circulatory death (DCD) Living donation Expanded criteria (EC) donors
What is ABO compatibility
avoids hyperacute rejection. Expressed on donor kidneys. Follows blood transfusion rules (except A2 kidney donors may be transplanted into O or B recipients if anti-A antibody titres are low). ABO incompatible transplantation can occur with immunosuppression - rituximab and plasma transfusion prior to transplantation. A to O is the most common incompatibility.
What is HLA antigen matching
Best HLA match (HLA-DR (class 2)>HLA-B (class 1)>HLA-A): reduces risk of acute rejection, improves graft survival, prevents allo-sensitisation. Less matching, increases chance of developing antibodies and rejection.
What are the different HLA classes
HLA class one in all nucleated cells. HLA class two in APCs and activated endothelial cells. Each px has 6 HLA (3 from each parent).
What is HLA
HLA are polymorphic antigens critical molecules for the presentation of foreign peptides to T cells. Located in the short arm of chromosome 6.
What does pre-formed anti-donor HLA antibody cuase
Hyperacute rejection. Presence is associated with a higher risk of antibody mediated rejection. Positive CDC T cell crossmatch is a contraindication for renal transplantation. De Novo DSA post-tx is major cause of graft loss
Who are at high risk of rejection
Px who are cross match negative but who have a current or historic donor-reactive antibody which has given arise following exposure to this antigen from a previous solid organ transplant or pregnancy.
Patients who are cross match positive by flow cytometry are deemed HLA antibody incompatible
How is immunosuppression given
Immunosuppression: first 3 months. Prevent production of HLA antibodies. Immunosuppression tapers slowly to maintenance levels by 6 to 12 months. Can cause infections and malignancy.
What are induction immunosuppression
Monoclonal antibodies: Basiliximab (anti-IL2 receptor), Alemtuzumab (anti-CD52)
Polyclonal antibodies: antithymocyte globulin
What are maintenance immunosuppression
Calcineurin inhibitors, tacrolimus, purine synthesis inhibitors, corticosteroid, mTOR inhibitors, fusion proteins, mycophenolate mofetil
What are the se of calcineurine inhibitors
cyclosporine (nephrotoxic effects, hypertension, glucose intolerance, dyslipidaemia, gum hyperplasia, hirsutism),
What are the se of tacrolimus
nephrotoxic effects, hypertension, glucose intolerance, T1DM, dyslipidaemia, hypomagnesaemia, tremor, hyperkalaemia, hair loss
What are the se of purine synthesis inhibitors
azathioprine (marrow suppression
What are the se of mycophenolate mofetil
diarrhoea GI upset, CMV infection
