Graft Vs Host Disease Flashcards
GvHD
- graft cells are immunocompetent
- host cells are foreign to graft
- host cells unable to eliminate graft cells
= donor cells mount response against host
Main cell involved in GvHD
T lymphocytes
- have longer lifespan (months - years)
Ie. CD4+ (Th1, Th2), CD8+, CD4+/CD25+ (T reg)
- also NK cells, APCs, B cells
GvHD is most commonly seen in which events ?
Allogeneic hematopoietic stem cell transplant > Solid organ transplant > Transfusion
GvHD: risk factors
- HLA mismatch
- age
- sex difference between donor & recipient
- female donor that’s had multiple births
- type of transplant (allogeneic > peripheral > hematopoietic stem cell)
- insufficient prophylaxis before transplant
- whole body radiation in chemotherapy
GvHD: acute vs chronic
Acute (3 phases):
1. APC activation (pre-transplant)
2. Donor T cell activation
3. Inflammatory phase
<100 days; within days
- higher mortality
- even fully matched HLA ( ie. twins)
Chronic:
>100 days
- complex, poorly understood
Describe Acute GvHD: Phase 1
- pre-transplant
- host primes own immune system; activation of APCs = host tissue damage (chemotherapy, radiation therapy, infection)
Acute GvHD: Phase 1 secretions and effect
- TNF-a
- IL-1B, IL-6
= fever, inflammation
= increased adhesion molecules, TNF-a receptors, MHC, activated APCs
Describe Acute GvHD: Phase 2
- donor T cells (immunocompetent) interact with host APCs = activation, proliferation, differentiation, migration
A. Direct = donor T cell recognizes host MHC
B. Indirect = donor APC presents host antigen to donor T cell
Describe Acute GvHD: Phase 2
- IL-2, IFNy, TNF-a
= CD8 and NK cells enhanced by IL-2
= increased MHC, integrins, L-selectins
Acute GvHD: Phase 3 secretions and effect
- donor T cytotoxic cells = tissue damage (ie. Fas-Fas, Perforin-granzyme)
- primed macrophages (host and donor) activated by LPS via TLRs on mucosa = produce TNF-a, IL-1, Nitric oxide = inflammation
GvHD symptoms
- fever
- rash; diapedesis
- diarrhea, vomiting, nausea
- liver dysfunction (increased bilirubin, ALP)
Transfusion related GvHD: symptoms
pancytopenia = infection
GvHD Prevention
- Prophylaxis (calcineurin inhibitors - cyclosporin, tacrolumis; methotrexate)
- For transfusions = irradiate cellular products
NOTE: anything frozen is not at risk of GvHD
Treatment for GvHD
- corticosteroids (immunosupression)
- anti-histamines
- manage infections/ supportive care
Chronic GvHD
- common in allogeneic hematopoietic stem cell transplants
- treatment = immunosuppression
Transfusion-related GvHD: risk factors
- pre-term infants
- primary immunodeficiencies (ie. SCID)
- immunosuppressed patients
- parental HLA match; If mom insists to be the donor, they are only partly HLA matched
