Solid Organ Transplants and Related Conditions

Vocabulary flashcards for reviewing key terms and definitions related to solid organ transplants, immunology, immunosuppression, and related conditions like Coeliac disease and Histamine intolerance.

Autograft

Transplantation of organs or tissues within the same person.

Allograft

Transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor.

Isograft

Transplantation of cells, tissues, or organs to a recipient from a genetically identical donor.

Xenograft

Transplantation of living cells, tissues, or organs from another species.

Cold Ischemia Time

The period when an organ is kept cold, without blood flow, from the time it's harvested from the donor to the time it's implanted into the recipient.

Inclusion/exclusion for transplantation

• Age → no strict exclusion

• Comorbidity → Unacceptable risk of mortality/morbidity during or after transplantation e.g. active malignancy

• Behavioural risk → Substance abuse

• Adherence with medications → cognitive deficiency / absence of carer

Organ allocation

• ABO blood type (antibody and Rh factor)

• Medical urgency

• Waiting list

• Georgraphy

Human Leukocyte Antigen (HLA)

The surface antigens on white blood cells that must be matched as closely as possible for organ transplant to avoid triggering an immune response.

6 antigens: A, B, C, D, DR

Cytomegalovirus (CMV)

A common opportunistic pathogen after transplant, which may be acquired from the donor or reactivation of a latent infection.

Pneumocystis Pneumonia

A type of pneumonia caused by Pneumocystis jirovecii, characterized by high fevers, dry cough, and minimal sputum production.

Respiratory Syncytial Virus (RSV)

A highly contagious virus that infects the airways and lungs, potentially causing permanent reduction in lung function.

Aspergillus

Fungal infection caused by inhaled spores; angioinvasion results in necrosis of tissue causing cavitation and coughing up blood.

Hyperacute Rejection

Rejection occurring within the first day of transplant due to incorrect blood type and HLA matching.

Acute Rejection

Rejection occurring days to months post-transplant, mediated by T-cytotoxic lymphocytes attacking the organ.

Risk factors for acute rejection

• 1 or more HLA mismatch

• older → younger recpipient

• Donor-specific antibody

• Cold ischemia time > 24 hours

Chronic Rejection

Rejection occurring months to years post-transplant, involving immune-mediated injury, ischemia-reperfusion injury, and immunosuppressive drug toxicity.

Induction Therapy

Therapy started around the time of transplantation with a greater dosage than maintenance therapy, used to prevent acute rejection.

Induction therapy consists of:

• Biological antibodies ATG (high risk rejection)

• Basiliximab (low risk rejection)

• high-dose glucocorticoids

Maintenance Therapy

Therapy started around the time of transplantation and continued long-term for the duration of the transplant to prevent rejection.

Maintenance Therapy consists of:

• Glucocorticoids

• Calcineuine inhibitors

• Antimetabolic agents

• mTOR

• Costimulatory blockade agents (betalactacept)

Anti-thymocyte Globulin (ATG)

• Rabbit

• An antibody against human T-cells → suppress

• X → live vaccines

Basiliximab

• An IL2 inhibitor → IL-2 induced T-cell proliferation

• X → live vaccines

Alemtuzumab

• A CD52 mAb

• Causes antibody-dependent cellular cytotoxicity → TB lysis

• X → live vaccines

Cyclosporine

• A calcineurin inhibitor → Lymphokine production

• Prevents T-cell proliferation

• ✅ → Vaccines

• CYP3A4 substrate → DDI

Tacrolimus

• A calcineurin inhibitor → lymphokine production

• Reduces T cell activation B cell proliferation

• ✅ → Vaccines

• CYP3A4 substrate → DDI

Everolimus

• An mTOR inhibitor that inhibits T-cell proliferation

• CYP3A4 substrate → DDI

• ✅ → Vaccines

Sirolimus

• An mTOR inhibitor that inhibits T-cell proliferation

• CYP3A4 substrate → DDI

• ✅ → Vaccines

Prednisolone

• Corticosteroids that suppress the inflammatory response.

• NO NSAIDs

• ✅ → Vaccines

Mycophenolic Acid

• An antimetabolite immunosuppressant

• Suppress T and B

• Inhibits inosine monophosphate dehydrogenase (IMPDH)??

• X → Live attenuated vaccines

Azathioprine

• An antimetabolite immunosuppressant

• 6MP → 5mMP reduces the proliferation of B and T

• TPMT and 6TGN → hepatoxicity

• X → Live attenuated vaccines

Valganciclovir

• A nucleoside analogue that stops viral DNA elongation used against CMV, HSV, Epstein-Barr virus (EBV), varicella-zoster virus, and hepatitis B virus.

• Avoid nephrotoxic drugs

Voriconazole

• Azole that inhibits fungal cytochrome P-450
  → fungal ergosterol biosynthesis.

Pneumocystis Jirovecci Prophylaxis and Trx

Prophylaxis

• T/S 960mg d

Trx

• T/S 30mg/kg d for 14 days

Bioequivalence

Must be 90% confidence interval