Organ Transplantation

what are human leukocyte antigens (HLA)

• major histocompatibility antigens (proteins encoded by genes)

• antigens responsible for rejection

what cells are HLA genes located

located on all nucleated cells and platelets

where are HLA genes located 

on chromosome 6 

are HLA genes polymorphic

yes, they are highly polymorphic (many alleles)

How many alleles are inherited for each HLA locus?

Two independent, codominant alleles (one from each parent).

What does codominant expression mean?

Both inherited alleles are expressed.

How are HLA alleles identified?

Each allele at each locus is numbered

what is a haplotype

The entire set of HLA genes on one chromosome, inherited as a unit.

how many haplotypes does each person inherit

two; one from each parent 

Which HLA genes are most important for compatibility testing

A, B, C, D or DR genes

what is the chance that two sibings will be a full HLA match

25 %

does the Rh factor need to match with for blood typing?

no

What does Human Leukocyte Antigen (HLA) typing evaluate?

A, B, and DR antigens (histocompatibility antigens)

How many HLA antigen matches are associated with better patient outcomes?

5–6 matches

organs that require the closest to the least HLA matching

bone marrow & kidneys > heart & lungs → cornea & liver

panel of reactive antibodies (PRA)

• shows the recipients sensitivity to HLA’s before transplant 

• detects preformed antibodies to HLA’s 

what are options for highly sensitized pts (high PRA)

plasmapheresis & IV immunoglobulins (IVIG)

lowers the number of antibodies 

what can cause deformed antibodies

blood transfusions, pregnancies, previous organ transplants

what is crossmatching

testing for existence of antibodies against potential donor

recipient serum + donor lymphocytes 

negative cross match

no performed antibodies

positive crossmatch

cytotoxic antibodies present

What is the exception to not proceeding with a positive crossmatch?

When no other options exist, plasmapheresis and IVIG can be used to reduce antibodies.

What role does crossmatching play in transplant care?

It helps guide immunosuppression protocols.

transplant rejection 

normal immune response to foreign tissue 

what reduces risk of rejection

• immunosuppression therapy

• ABO & HLA matching 

• negative crossmatch 

what is the best match for transplants

• tissue from self 

• identical twin 

• sibling 

types of rejection

hyperacute

acute 

chronic 

hyperacute rejection

• occurs within 24 hours of transplant 

• preexisting antibodies 

treatment for hyperacute rejection

no treatment, remove the organ

is hyperacute rejection common?

no, rare because of more effective immunosuppressants and improved screening 

what prevents hyperacute rejection from occuring

Final crossmatch testing, which detects sensitization (preformed antibodies).

acute rejection

• first 6 months after transplant 

• cell-mediated immune response 

• humoral immune response 

What happens during cell-mediated acute rejection?

The recipient’s lymphocytes attack the donated organ

What is humoral (antibody-mediated) acute rejection?

When the recipient develops antibodies against the donated organ.

Is it common for transplant recipients to experience at least one acute rejection episode?

yes 

is acute rejection irriversible?

yes with additional immunosuppressants 

what is a complication of increasing immunosuppression

increased risk for infection

what can treat acute rejection

• corticosteroids 

• polyclonal antibodies 

• monoclonal antibodies 

chronic rejection

• over months or years after the transplant 

• repeated episodes of acute rejection 

• lifelong balance between rejection & infection 

is chronic infection reversible?

no

Which immune cells infiltrate the transplanted organ during chronic rejection?

T & B cells 

What type of injury occurs in chronic rejection?

Ongoing, low-grade, immune-mediated injury that leads to fibrosis and scarring.

What is the chronic rejection complication in heart transplants?

Accelerated cardiovascular disease

What complication occurs in chronic liver rejection?

loss of bile ducts 

Q: What complication occurs in chronic kidney rejection?

fibrosis and glomeruolopathy

Q: What complication occurs in chronic lung rejection?

bronchoiolitis obliterans

treatment for chronic rejection

None, treatment is supportive

What is the goal of immunosuppressive therapy after a transplant?

• prevent rejection 

• minimize infection 

• minimize development of cancer 

what is “triple therapy”

• multiple drugs that target different phases of the immune response

• multiple drugs at lower dose to decrease side effects 

calcineurin inhibitors

prevent a cell-mediated attack

• tacrolimus (Prograft) 

• cyclosporine (Sandimmune) 

corticosteroids

reduce inflammation and suppress immunity

• prednisone

• methylprednisone

purine synthesis agonists

inhibit purine synthesis needed for lymphocyte proliferation

• mycophenolate mofetil (CellCept)

• azathioprine (Imuran)

sirolimus

suppresses T cell activation

• sirolimus (Rapamune)

what drugs prevent early rejection/reverse acute rejection and their side effects

• Muromonab-CD3

  • Monoclonal antibodies (flu-like symptoms)

• Anithymocyte globulin

  • Polyclonal antibodies (leukopenia, thrombocytopenia)

graft-versus-host disease

• immunodeficient host receives immunocompetent cells

• graft (donated) tissue rejects the host (recipient tissue) 

which type of transplant is GVHD most common 

hematopoietic stem cell transplants 

when does GVHD happen?

7-30 days after transplant

what cells attack host cells in GVHD?

donor T cells attack host cells

manifestations of GVHD

• skin → maculopapular rash: palms, soles of feet, general desquamation) 

• liver → jaundice 

• GI tract → diarrhea, pain, bleeding 

early vs later infection in GVHD?

early → bacterial and fungal

later → interstitial pneumonitis

complications of organ transplant

• ischemia 

• vascular thrombosis 

• bleeding 

• anastomosis leakage 

• infection 

ischemia in organ transplant

delay in transplanting donor organ after harvesting (hypoxic injury) 

vascular thrombosis in transplanted organ

• blood clot in vasculature of graft

• diagnosed with ultrasound ; treated with thrombectomy

anastomosis leak

leakage at the surgical connection site between donor and recipient tissues 

• requires surgical repair 

signs of infection after organ transplant 

low grade fever

discomfort 

mental status change 

infection control measures for organ transplant

• hand hyegeine 

• reverse isolation 

• restrict visitors who are ill 

what should you monitor to prevent infection

temperature

localized (wound) 

systemic (pneumonia ; sepsis) 

signs of rejection

• weight gain

• edema

• extra heart sounds

• fever

• tachycardia

signs of sepsis

• fever 

• tachycardia 

• lymphadenopathy 

• cloudy urine 

• malaise 

• change in sputum