lecture 20 - monoclonal antibody in solid organ transplant

What is transplant rejection?

An adaptive immune response where the recipient’s immune system attacks transplanted tissue.

Which immune cells are involved in transplant rejection?

• T cells (cellular immunity): Cause apoptosis of donor cells.

• B cells (humoral immunity): Produce antibodies leading to cytotoxicity.

What types of transplants are usually not rejected?

Cornea transplants (immune-privileged) and identical twin transplants.

What is direct allorecognition?

Donor dendritic cells present antigens directly to recipient T cells.

What is indirect allorecognition?

Recipient dendritic cells process and present donor antigens to recipient T cells.

What are immune checkpoints in transplant rejection?

Signals that regulate T cell activation during immune response.

Give examples of stimulatory and inhibitory immune checkpoints.

• Stimulatory: CD28, ICOS, CD137

• Inhibitory: PD1, CTLA-4, VISTA

What are some adverse effects of current immunosuppressants?

Hypertension, hyperlipidemia, hyperglycemia, renal dysfunction.

What long-term effect is associated with calcineurin inhibitors?

Kidney damage.

Why are monoclonal antibodies used in transplant medicine?

To provide safer alternatives and targeted immune modulation.

What is Rituximab’s target and use in transplant?

Targets CD20 on B cells; used for pre-transplant desensitization and treating PTLD and antibody-mediated rejection.

What does Alemtuzumab target and when is it used?

Targets CD52; used for induction in pancreas and intestinal transplants.

What is the function of Daclizumab and Basiliximab?

Target CD25 (IL-2 receptor); block T cell activation. Basiliximab is more potent

What is Eculizumab’s target and clinical use?

Targets C5 complement; treats atypical HUS and antibody-mediated rejection post-transplant.

What are corticosteroids’ mechanism of action?

Bind to cortisol receptors and regulate gene expression.

How do NSAIDs reduce inflammation?

Inhibit COX enzymes → ↓ prostaglandins → ↓ pain & inflammation.

What are examples of conventional DMARDs?

Methotrexate, azathioprine, sulfasalazine.

What cytokines are key in RA pathophysiology?

TNF-α, IL-1, IL-6.

clinical use of mAbs

• Pre-transplant (Desensitization)

  • Rituximab (CD20): Remove pre-existing antibodies (for ABO-incompatible or highly sensitized patients).

• At Transplant (Induction Therapy)

  • Alemtuzumab (CD52): Profound T-cell depletion.

  • Daclizumab, Basiliximab (CD25): Block IL-2 receptor → prevent T-cell activation

  • Goal: Reduce corticosteroid/calcineurin inhibitor usage.

• Post-transplant (Rejection Treatment)

  • Eculizumab (C5): Inhibits complement-mediated injury (eg. aHUS, AMR).

  • Muromonab-CD3: Targets T cells directly (no longer commonly used).

daclizumab use

Kidney transplant rejection prevention (induction)

induction drugs

daclizumab

basiliximab

alemtuzumab

desensitization drug

rituximab

rejection drug (post)

eculizumab