Medical Archive

Background

Definitions

Autograft: from self
Isograft (syngeneic graft): from identical twin or clone.
Allograft: from nonidentical indivicual of same species.
Xenograft: from different species.

History

Transplant immunobiology

Transplant Antigents

Allorecognition and lymphocyte activation

Clinical rejection

Hyperacute
Type II, widespread thrombosis
Arterial fibrinoid necrosis & capillary thrombotic occlusion
Minutes to hours

Acute
Type IV, vasculitis of graft vessels.
Cellular: lymphocytic interstitial infiltrate & endotheliitis
Humoral: C4d deposition, neutrophilic infiltrate, necrotizing vasculitis
Usually <6 months

Chronic
Type II & IV, dominated by arteriosclerosis.
Vascular wall thickening & luminal narrowing, interstitial fibrosis & parenchymal atrophy
Bronchiolitis obliterans (lung), accelerated atherosclerosis (heart), chronic graft nephropathy (kidney), vanishing bile duct syndrome (liver) 
Months to years.

GVHD
Type IV, onset varies.
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly. Usually in bone marrow, liver transplants (rich in lymphocytes)
Potentially beneficial in leukemia (graft-versus-tumor effect)

Clinical immunosuppression

Steroid		?? ?? ??
CNI	Cyclosporine, Tacrolimus	T lymphocyte ??? ??
Anti-proliferation	MMF, Azathioprine
mTOR inh.	Sirolimus, Everolimus
ATG-R	Thymoglobulin, ATGAM
Anti-CD25(IL-2R)	Baxiliximab (simullect)
Anti-CD20	Rituximab

Drugs	Mechanism	Other use	Toxicity	Notes
Cyclosporine	CNI  (binds cyclophilin)	Psoriasis, rheumatoid arthritis	Nephrotoxicity, neurotoxicity, gingival hyperplasia, hirsutism, DM, hyperlipidemia	Both CNI are highly nephrotoxic.
Tacrolimus (FK506)	CNI  (binds FKBP)		?risk of DM and neurotoxicity; no gingival hyperplasia or hirsutism.
Sirolimus (rapamycin)	mTOR inhibitor (binds FKBP)	Kidney tranplant rejection prophylaxis, DES	Pancytopenia, DM, hyperlipidemia	Synergistic with cyclosporine
Basiliximab	Monoclonal Ab	Kidney tranplant rejection prophylaxis	Edema, hypertension, tremor
Azathioprine	Precursor of 6-MP Blocks PRPP?IMP	Rheumatoid arthritis, Crohn disease, glomerulonephritis, other autoimmune conditions.	Pancytopenia	6-MP degraded by xanthine oxidase (?toxicity by allopurinol)
Mycophenolate mofetil	Blocks IMP?GMP	Lupus nephritis	Pancytopenia, GI upset, hypertension, DM.	Associated with invasive CMV infection.
Glucocorticoid	Inhibit NF-?B. Induce T cell apoptosis.	Many others, including adrenal insufficiency, asthma, CLL, non-Hodgkin lymphoma	Cushing syndrome, osteoporosis, DM, amenorrhea, adrenocortical atrophy, peptic ulcer, psychosis, cataracts, avascular necrosis of femoral head.	Demargination of WBCs causes artificial leukocytosis.

• Acute rejection treatment
  • Steroid pulse therapy
  • OKT3 (anti-CD3 monoclonal Ab)
  • ATG (anti-thymocyte globulin)
• Acute rejection prevention
  • Cyclosporin A + Steroid + Azathioprine

Induction

Depleting antibodies

Non-depleting antibodies

Maintenance

Corticosteroids

Azathioprine

Mycophenolate mofetil

Sirolimus

Cyclosporine

Tacrolimus

Belatacept

Humoral rejection

Rituximab

Bortezomib

Eculizumab

Infections and malignancies

Infections

Early

Late

# Prophylaxis

• TMP-SMX for PCP in patients who have had solid organ transplantation.
  • Efficacy against most strains of L.monocytogenes and Toxoplasma gondii
  • Patients can often stop 6-12 months after transplant because immunosuppressive regimens are generally tapered over time.
• Many patients also require CMV prophylaxis with ganciclovir or valgagnciclovir
• Fungal prophylaxis with itraconazole in lung & liver transplantation

Malignancies

Organ procurement and preservation

1. a. Procurement (Harvest)
   • • Donor? ?? ????? ?? ?? ??

??? ??? ????

Heart

Lung

Liver

Pancreas

kidney

1. b. Donor management

1. i. ?? ???? ?? – ????
   KODA ?? ? 6(48, 24)?? ???? ???? ?? ? 30?? ?? ?? 1(2, 1)?
   ?? ?? ?? ?? = ?? ????
2. c. Transplantation Immunology (?? ?? ??)

Kidney transplantation

Ix: CKD stage 4~5

ABO typing
HLA X-match (???? ???)
± Lympho-cytotoxic X-match (?? ???)

Post-KT management

??? ?? 1,000cc/hr? ??? ??. Half saline + 30mEq/L NaCO3? ??!
Hypervolemic: Irrigation ? Furosemide ? Doppler or scan ? exploration
Hypovolemic: N/S 250~500mL ? U.O. ???? continue half saline

Acute rejection

Diagnosis

1. Symptom
   • ??? Cx?? ??? m/c (blood clot? m/c?? ??? ?? ??)
   • ?? ?? ??? Cr??? ??? ?????.
2. Serial Doppler US, renal scan
   • ?? ??, obstruction r/o
   • ATN? renal blood flow? ??, rejection ?? RBF ??.
3. Percutaneous needle aspiration Bx
   • Acute rejection? ??

Pancreas transplantation

????

??: amylase ?

??: ?? ?

• Cx: ???, ?? ??
• ????(PTA), ?? ? ??(PAK)?? ?? ??(SPK)? ??

Islet transplantation

Liver transplantation

Harrison C338

Intestine and multivisceral transplantation

• Ix: short bowel syndrome. ??? ischemia, ??? gastroschisis? m/c
• ????? gastroenteritis? ????, ??? marker? ??

Heart and lung transplantation

Xenotransplants