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Transplantation medicine Flashcards

1
Q

What is an autograft?

A

Transfer of living cells, tissues or organs from one part of the body to another

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2
Q

What is an allograft?

A

Transfer of living cells, tissues or organs from one individual to another individual of the same species

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3
Q

What is a xenograft?

A

Transfer of living cells, tissues or organs from one individual to an individual of another species

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4
Q

What is an allo-immune response?

A

Immune response to non-self-antigens from members of the same species

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5
Q

What are the main players in allo-immune responses?

A
  1. APCs
  2. T-cells (can lead to cellular rejection & activate B-cells)
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6
Q

What are allo-antigens?

A

All antigens that differ between individuals of the same species

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7
Q

What are important groups of allo-antigens in organ transplantation? (3)

A
  1. Major histocompatibility complex antigens
  2. Minor histocompatibility complex antigens
  3. Blood group antigens
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8
Q

What type of rejection will a mismatch in major histocompatibility antigens cause?

A

Fast and strong rejection

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9
Q

What type of rejection will a mismatch in minor histocompatibility antigens cause?

A

Chronic rejection -> slow & weak

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10
Q

Where are the MHC-antigens encoded?

A

P-arm of chromosome 6

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11
Q

Why are there so many MHC mismatches between individuals?

A

Highly polymorphic gene locus with various alleles -> lot of variety in population

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12
Q

Which two types of minor allo-antigens can be identified?

A
  1. All proteins that differ in amino acid composition between donor and recipient (for instance due to genetic mutations, polymorphisms)
  2. Y-chromosome encoded proteins (if transplanting from man to woman)
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13
Q

How do proteins that differ in amino acid composition cause rejection?

A

They are presented in MHCII to T-cells -> these cells recognize the small differences from self-antigens

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14
Q

Why do blood group antigens cause rejection?

A

T-cell independent B-cell activation due to recognition of repeated sugar structures by BCR

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15
Q

Which three pathways can lead to allo-antigen presentation? Which of these three is most important in organ rejection?

A
  1. Direct allo-recognition = most important
  2. Indirect allo-recognition
  3. Semi-direct allo-recognition
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16
Q

What is direct allo-recognition?

A

Recognition of intact foreign molecules on APCs of donor

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17
Q

Which cells get activated by direct allo-recognition?

A

T-cells -> cross-react with intact foreign HLA-molecules -> T-cell activation

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18
Q

Which two forms of direct allo-recognition are there?

A
  1. Direct activation of TCR by intact foreign MHC, without peptide -> stronger response
  2. Activation of TCR by non-self peptide being recognized in non-self MHC
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19
Q

What is indirect allo-recognition?

A

Recognition of donor HLA peptide by recipient HLA-molecule on recipient APC (very small response)

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20
Q

What is semi-direct allo-recognition?

A

Recognition of intact donor HLA + peptides on recipient APC

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21
Q

How do APCs acquire donor HLA with donor peptide in case of semi-direct allo-recognition?

A

Cleaving HLA off at the membrane and taking over the loaded HLA-complex from the donor cell

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22
Q

What kind of reaction is induced by allo-antigen stimulation?

A

Recipient T-cells primed by donor HLA in recipient organs migrate to graft & cause damage to cells expressing donor HLA

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23
Q

T-cell rejection due to allo-antigen presentation is most important [early/late] after transplantation. Why?

A

Early -> during late stage, recipient APCs replace donor APCs, leading to an absence of donor APCs to activate the direct pathway

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24
Q

How can allo-immune responses be analyzed?

A

Cross-reactivity test

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25
Q

How does a cross-reactivity test for allo-antigen recognition work?

A

Blood from patient + blood/splenocytes from donor mixed -> then studying T-cell activation using flow cytometry for cytokine/activation markers

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26
Q

In which case is donor blood, and in which case are donor splenocytes used for a cross-reactivity test?

A

Blood = living donor
Splenocytes = deceased donor

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27
Q

How can you make sure you analyze only the recipient immune response in a cross-reactivity test?

A

Irradiating the donor cells before the test -> prevents them from proliferating and attacking recipient cells

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28
Q

What are clinical signs of kidney rejection? (2)

A
  1. Rise in creatinine (decrease of eGFR)
  2. Decrease in urine production
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29
Q

How is kidney rejection confirmed?

A

Kidney biopsy

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30
Q

What is unique about liver transplantation? (2)

A
  1. Partial transplantation is possible (living donor retains part of their liver that will grow back)
  2. No HLA matching required
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31
Q

What are signs of liver transplant rejection? (4)

A
  1. Fever
  2. Fatigue
  3. Abdominal pain
  4. Decreased liver function
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32
Q

What markers are used to show liver function? (3)

A
  1. ALAT/ASAT (increase in case of liver damage)
  2. Alkaline phosphatase (increases in case of liver damage)
  3. Bilirubin (increases in case of liver damage)
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33
Q

True or false: troponins/NT-proBNP can be used to gauge rejection of transplant hearts

A

False; there are no good biochemical measurements for heart rejection

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34
Q

How are donor hearts checked for rejection after transplantation?

A

Regular biopsies

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35
Q

On which cells are ABO-blood group antigens present? (3)

A
  1. Erythrocytes
  2. Endothelial cells
  3. Tubular cells (kidney)
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36
Q

What happens in case of ABO-incompatible transplant?

A
  1. Blockages in capillaries
  2. Hyperacute rejection
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37
Q

What is hyperacute rejection?

A

Organ loss in minutes/hours after transplantation due to severe damage by anti-ABO antibodies

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38
Q

True or false: all HLA-molecules are equally important for transplant rejection

A

False

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39
Q

Which HLA-molecules are generally most important for organ rejection? (3)

A
  1. A1
  2. B
  3. DR
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40
Q

Reactions against HLA-mismatch can be caused by donor reactive antibodies. How can these antibodies be present before rejection? (3)

A
  1. Induced by pregnancies
  2. Induced by blood transfusion
  3. Induced by earlier transplantation
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41
Q

How does the cross-reactivity test for HLA antibodies work?

A

Incubation of donor cells with patient serum -> in case of donor-reactive antibodies, lysis of cells will occur

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42
Q

Why is cross-matching for HLA antibodies not performed in heart transplantation?

A

Not enough time for cross-matching -> only HLA-typing

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43
Q

Why does the liver not require cross-matching or HLA typing?

A

Tolerogenic characteristics of the liver prevent rejection based on HLA-mismatch

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44
Q

True or false: a perfect HLA-match is required for succesful kidney/lung transplantation

A

False; match needs to be the best possible, but not perfect

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45
Q

All transplant organs have some degree of tissue damage. Why is this disadvantageous? (2)

A
  1. Loss of organ function
  2. Tissue injury leads to inflammatory injury
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46
Q

What does ischaemia reperfusion injury cause? (4)

A
  1. Reactive oxygen species
  2. Induction of cellular damage
  3. Release of inflammatory cytokines & chemokines
  4. Attraction & attachment of immune cells
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47
Q

How do BDD and CDC donors cause damage to the donor organs before removal?

A

BDD: cytokine storm, affecting donor organs
CDC: disturbance in blood supply, causing warm ischaemia

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48
Q

How is ischaemia reperfusion injury reduced?

A

Machine perfusion of organs

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49
Q

What happens during machine perfusion of organs?

A

Organs are supplied with oxygen, nutrients & temperature control

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50
Q

Which fluid is often used for machine perfusion of organs?

A

Donor blood

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51
Q

Which three types of organ rejection can be distinguished?

A
  1. Hyperacute rejection
  2. Acute rejection
  3. Chronic rejection
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52
Q

Which cells are first activated in acute rejection? How?

A

T-cells, activated by donor APCs migrating to the lymph nodes

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53
Q

What is the effect of T-cell activation in acute rejection? (2)

A
  1. Tc-cells cause direct damage to graft through lysis of cells
  2. Th-cells induce antibody production by B-cells
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54
Q

How do antibodies produced by B-cells activated by Th-cells in acute rejection contribute to rejection?

A

Cause antibody-mediated rejection (AMR) -> complement-mediated lysis of target cells

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55
Q

Which processes of acute rejection take place in the lymph node, and which in the organ?

A

Lymph node: activation of Th- and B-cells by donor APCs
Organ: cytotoxic T-cells, antibodies & complement

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56
Q

What are risk factors for acute cellular rejection? (5)

A
  1. Young age of recipients
  2. Female gender (both donor & recipient)
  3. High number of mismatches
  4. Black recipients
  5. Induction therapy
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57
Q

What are risk factors for antibody-mediated rejection? (5)

A
  1. Female gender
  2. Elevated pre-transplant PRA
  3. CMV seropositivity
  4. Previous implantation of ventricular assist device (VAD)
  5. Retransplantation
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58
Q

What is the first-line treatment of acute cellular rejection?

A

High dose methylprednisolone

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59
Q

What is the second-line treatment of acute cellular rejection?

A

Anti-thymocyte globulin (alemtuzumab) -> depletion of T-cells

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60
Q

What is the treatment of antibody-mediated rejection? (3)

A
  1. Plasmapheresis
  2. IVIG
  3. Rituximab (anti-CD20) -> depletion of B-cells
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61
Q

What is chronic rejection?

A

Slow deteroriation of organ function

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62
Q

What are the clinical signs of chronic rejection of the kidney? (3)

A
  1. Increase in serum creatinine (decrease in eGFR)
  2. Proteinuria
  3. Hypertension
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63
Q

Which changes can be observed in chronically rejected kidneys? (3)

A
  1. Interstitial fibrosis without evidence of any specific aetiology
  2. Ischaemia/cell death
  3. No massive infiltration of inflammatory cells
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64
Q

What is the major cause for kidney loss after transplantation?

A

Chronic rejection

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65
Q

What are hypotheses for the cause of chronic rejection? (2)

A
  1. Continuous low-level inflammation in the organ
  2. Chronic calcineurin inhibitor nephrotoxicity
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66
Q

What is the treatment for chronic rejection?

A

No treatment available to prevent organ damage -> only retransplantation can restore organ function

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67
Q

Which possibilies are currently studied to minimize/prevent chronic rejection? (6)

A
  1. Calcineurin inhibitor minimalization
  2. Using MMF instead of AZA
  3. mTOR inhibitors to prevent SMC proliferation
  4. ACE inhibitors to prevent hypertension
  5. Statins to prevent hyperlipidaemia
  6. Anti-oxidant vitamins to prevent oxidant stress
68
Q

Which HLA-molecules are important for stem cell transplantation?

A

All HLA-molecules (A, B, C, DR, DP, DQ)

69
Q

How are HLA-genes inherited?

A

One haplotype from both parents

70
Q

What is a haplotype?

A

One string of HLA-molecules, located on the same chromosome and therefore inheritec as a block

71
Q

Why are parents always haploidentical donors?

A

Children receive 1 haplotype from their parents -> parents always share at least 1 haplotype

72
Q

What is the chance of siblings being haploidentical donors?

73
Q

What is the chance of siblings being HLA-identical donors?

74
Q

What are the consequences of HLA-mismatching in transplantation?

A
  1. Host-versus-graft -> rejection of graft
  2. Graft-versus-host -> reaction of graft cells to host (only in stem cell transplantation)
75
Q

Which techniques can be used for HLA-typing? (2)

A
  1. Low resolution: PCR with primers for HLA locus
  2. High resolution: NGS/nanopore
76
Q

HLA typing takes place in [recipient/donor/both]

A

Both donor and recipient are HLA-typed

77
Q

HLA-antibody screening takes place in [recipient/donor/both]

A

Only in recipient

78
Q

How often is HLA-antibody screening performed? Why is it performed multiple times?

A

When patients are placed on the waiting list and then:
For solid organ tranpslantation: every 3 months + every time there are immunizing events
For stem cell transplantation: within 30 days of stem cell transplantation + every time there are immunizing events

This is necesarry because patients can develop antibodies whilst on the waiting list, for instance due to blood transfusions, vaccines, etc.

79
Q

How can flow cytometric crossmatching be performed?

A

Patient serum + donor blood/spleen + anti-IgG-FITC -> shows IgG binding to cells, proving reactivity of recipient antibodies to donor cells

80
Q

Why is the use of splenocytes preferred over blood in crossmatching?

A

Donor spleen contains more B-cells

81
Q

Why are renal biopsies performed after kidney transplantation? (5)

A
  1. Provides diagnosis (in case of rejection)
  2. Guides treatment
  3. Predicts diagnosis
  4. Reveals pathogenesis based on molecular & cellular mechanisms
  5. Validates outcome (in clinical trials)
82
Q

What are pitfalls in nephropathology? (6)

A

1 Diverse pathogenic mechanisms may produce similar morphological response
2. Small size of biopsy
3. Primary lesions not always easy to find
4. Progression to end-stage disease results in non-specific chronic changes that obscure original pathological processes
5. Experience of pathologist very influential
6. Sampling error

83
Q

Which information is important for renal pathologist to be able to interpret pathology? (7)

A
  1. Donor source
  2. Time post-transplantation
  3. Initial kidney function
  4. Current renal function
  5. Drug therapy
  6. Original disease
  7. Anti-donor HLA antibodies
84
Q

Which groups of diseases are commonly found in transplanted kidneys? (4)

A
  1. Rejection
  2. Drug toxicity
  3. Viral infection
  4. Donor disease
85
Q

What is the Banff classification?

A

Classification for transplant kidneys

86
Q

What is the advantage of the Banff classification?

A

Standardized; allows for multi-centre trials

87
Q

What is the minimum of features that has to be present to judge a kidney biopsy according to the Banff classification?

A

7 glomeruli & 2 arteries

88
Q

What are the types of rejection in the Banff classification?

A
  1. Acute T-cell mediated rejection (aTCMR) -> T-cells
  2. Acute antibody mediated rejection (AMR) -> NK-cells, macrophages & monocytes, spurred on by antibodies/complement
89
Q

What are the subtypes of aTCMR? (4)

A
  1. Suspicious/borderline
  2. Tubulo-interstitial
  3. Endarteritis
  4. Transmural inflammation/fibronoid necrosis
90
Q

How many % of suspicious/borderline cases of aTCMR develop into rejection?

91
Q

What is the morphology of type 1 (tubulo-interstitial) aTCMR?

A

Lymphocyte infiltration

92
Q

What does granulocyte infiltration in kidney biopsy point to?

A

Pyelonefritis (not characteristic of rejection)

93
Q

What is the pitfall of diagnosing tubulo-interstitial aTCMR?

A

Looks similar to polyoma- or CMV-infections

94
Q

What is BK-nephropathy?

A

Polyoma infection of the kidney

95
Q

How can BK-nephropathy be distinghuished from tubulo-interstitial aTCMR? (2)

A

Histology: presence of plasma cells points to BK-nephropathy
Serology: polyoma antibodies

96
Q

What is the morphology of type 2 (vascular rejection) aTCMR?

A

Inflammatory rejection in the arterial endothelium, presence of lymphocytes

97
Q

What is the histological picture of aBMR? (4)

A

Acute tissue injury, seen as:
1. Tubular injury
2. Neutrophils in peritubular capillaries -> microvascular injury
3. Thrombi
4. Fibrinoid necrosis

98
Q

How can immunohistochemistry be used to show aBMR?

A

Deposition of C3, C4b and antibodies in peritubular capillaries

99
Q

True or false: calcineurin inhibitor toxicity can not be distinguished from rejection

A

False; calcineurin inhibitor toxicity leads to characteristic morphological changes

100
Q

Which three regimens of immunosuppression are used in kidney transplantation?

A
  1. Induction therapy
  2. Maintenance therapy
  3. Anti-rejection therapy
101
Q

What is the goal of induction therapy in organ transplantation? Which drugs are used?

A

Prevention of activation of immune reaction
Drugs: basiliximab

102
Q

What is the goal of maintenance therapy in organ transplantation? Which drugs are used?

A

Maintaining tolerance to graft
Drugs: tacrolimus, mycophenolate mofetil, prednisolon

103
Q

What is the goal of anti-rejection therapy in organ transplantation?

A

Suppression of acute rejection

104
Q

To which class of drugs does tacrolimus belong? What is its mechanism of action?

A

Calcineurin inhibitors -> block downstream signaling of the TCR

105
Q

What is the mechanism of action of mycophenolate mofetil? What is its brand name?

A

Mechanism of action: blocking of nucleoside synthesis and therefore expansion of immune cells
Brand name: Cellcept

106
Q

What is the mechanism of action of prednisolon?

A

Blocks transcription of inflammatory genes

107
Q

At which points in the immune rejection are drugs in organ transplantation aimed? (5)

A
  1. Signal 1: TCR activation
  2. Signal 2: costimulation
  3. Signal 3: inflammatory cytokines
  4. Immune cell proliferation
  5. Immune cells
108
Q

Which drugs used in organ transplantation target signal 1?

A

Calcineurin inhibitors -> inhibit downstream signaling of TCR

109
Q

Which drugs are part of the calcineurin inhibitors? (2)

A
  1. Tacrolimus
  2. Cyclosporine
110
Q

What is the mechanism of action of mTOR inhibitors?

A

Blocking of immune cell proliferation

111
Q

Which drugs belong to the mTOR inhibitors? (2)

A
  1. Everolimus
  2. Sirolimus
112
Q

Why can azathioprine be used in organ transplantation?

A

It inhibits proliferation of inflammatory cells through blockages of the cell cycle

113
Q

What is the mechanism of action of anti-CD52 monoclonals?

A

Deplete T-cells -> stops immune reactions

114
Q

What are common side effects of immunosuppressive drugs used in organ transplantation? (4)

A
  1. Reactivation of infections
  2. Malignancies due to depressed immune activation
  3. Cardiovascular disease
  4. Hyperglycaemia due to steroids
115
Q

What are side effects of prednisolone? (6)

A
  1. Hypertension
  2. Increased hair growth
  3. DM
  4. Increased cholesterol
  5. Muscle weakness
  6. Obesity
116
Q

What are side effects of tacrolimus? (6)

A
  1. Hypertension
  2. Decreased hair growth
  3. DM
  4. Nephrotoxicity
  5. Neurotoxicity
  6. Increased cholesterol
117
Q

What are side effects of cyclosporine? (6)

A
  1. Hypertension
  2. Increased hair growth
  3. DM
  4. Nephrotoxicity
  5. Neurotoxicity
  6. Increased cholesterol
118
Q

What are side effects of azathioprine? (3)

A
  1. Hepatotoxicity
  2. Bone marrow toxicity
  3. Abdominal complaints/diarrhoea
119
Q

What are side effects of MMF? (2)

A
  1. Bone marrow toxicity
  2. Abdominal complaints
120
Q

What are side effects of sirolimus/everolimus? (6)

A
  1. Nephrotoxicity
  2. Ulcerations in the mouth
  3. Increased cholesterol
  4. Hepatotoxicity
  5. Bone marrow toxicity
  6. Abdominal complaints/diarrhoea
121
Q

How are infections prevented during immunosuppressive therapy? (5)

A
  1. Vaccinations before transplantation
  2. Anti-bacterial prophylaxis: cotrimoxazole for PJP
  3. Anti-viral prophylaxis: valgancyclovir for CMV
  4. Tapering immunosuppression
  5. Life-style advice
122
Q

How are malignancies prevented/managed under immunosuppressive medication? (2)

A
  1. Population screening
  2. Tapering immunosuppression
123
Q

How can cardiovascular disease be prevented under immunosuppressive medication? (2)

A
  1. Steroid-free regimen
  2. Tapering tacrolimus (but: higher risk of rejection)
124
Q

Why does tacrolimus require especially tight drug monitoring?

A

Small therapeutic window & high interindividual variance of metabolism

125
Q

Why does MMF especially increase risk of viral infection?

A

Specifically inhibits antiviral immunity

126
Q

Which groups of drugs can be used if a calcineurin inhibitor-free regimen is desired? (2)

A
  1. Costimulation blockers
  2. mTOR inhibitors
127
Q

Which costimulation inhibitors are available in organ transplantation settings? (2) Which costimulatory mechanisms do they block?

A
  1. Belatacept -> CD80/CD86 - CD28 interaction
  2. Iscalimab -> CD40-CD154 interaction
128
Q

What is the disadvantage of using belatacept?

A

Increases risk of lymphoma/EBV infections

129
Q

Why is iscalimab not used in organ transplantation?

A

Severe side effects

130
Q

Why is it desirable to use cellular therapies in organ transplantation? (3)

A
  1. Less side effects than current therapies
  2. Long-term effects -> cells may be around for a long time
  3. Cellular therapy may create a balance between activation & suppression
131
Q

Which immune cells with regulatory functions can be found within the myeloid lineage? (3)

A
  1. Myeloid-derived suppressor cells
  2. Regulatory macrophages (M2)
  3. Tolerogenic DCs
132
Q

Which immune cells with regulatory functions can be found within the lymphoid lineage? (4)

A
  1. CD4+ regulatory T-cells
  2. CD8+ regulatory T-cells
  3. γδ T-cells
  4. Regulatory B-cells
133
Q

What is the main role of myeloid regulatory cells?

A

Tissue homeostasis by dampening immune responses through effects on the T-cell compartment

134
Q

How are regulatory macrophages induced?

A

Costimulation of activated macrophages by regulating cytokines

135
Q

What are tolerogenic DCs

A

DCs with a weak costimulation -> induce Tregs

136
Q

What are mesenchymal stem cells (MSCs)?

A

Stem cells of connective tissues

137
Q

Into which major cell types do MSCs differentiate? (4)

A
  1. Osteoclasts
  2. Adipocytes
  3. Chondrocytes
  4. Fibroblasts
138
Q

From which kinds of connective tissue are MSCs currently harvested? (2)

A
  1. Bone (hip replacement bone, bone marrow aspiration)
  2. Adipose tissue
139
Q

MSCs are [easily expanded/difficult to expand] after harvesting

A

Easily expanded -> harvesting of a few thousand MSCs can be cultured in to a large population

140
Q

What is the immunomodulatory function of MSCs?

A

Suppression of inflammatory cell types via soluble and non-soluble signaling

141
Q

What are important players in immunomodulatory functions of MSCs? (2)

A
  1. PD-L1 = co-inhibition
  2. IDO -> depletes L-tryptophan, which is needed for lymphocyte proliferation
142
Q

In which environments are the immunomodulatory effects of MSCs strongest?

A

Inflammatory environments

143
Q

Where do MSCs end up when they are injected intravenously?

A

Lung capillaries -> first capillary bed they encounter

144
Q

How long do MSCs remain present after IV administration? How are they cleared?

A

~1 day, cleared through phagocytosis by macrophages

145
Q

What hypothesis is used to explain why MSCs have immunomodulatory effects, even if they are cleared within 1 day?

A

Macrophages that clear them adopt a regulatory phenotype and induce a higher amount of Tregs

146
Q

What are the advantages of using allo-MSCs vs. auto-MSCs? (2)

A
  1. Allo-MSCs can be used clinically without delay required for expansion
  2. Allo-MSCs could elicit anti-donor immune response, thus increasing graft loss
147
Q

What are important markers of CD4+ Tregs?

A

Extracellular: IL-2R/CD25+
Intracellular: FoxP3

148
Q

Why is it hard to isolate a population of Tregs for clinical use?

A

FoxP3 can only be stained for intracellularly -> cells are not viable anymore after staining

149
Q

By which mechanism do Tregs regulate immune responses in the thymus?

A

Deletion of auto-reactive T-cells

150
Q

By which mechanisms do Tregs regulate immunity in the periphery? (4)

A
  1. Cell-cell contact: by competing for costimulating between effector T-cells and APCs
  2. Secreting inhibitory cytokines
  3. Cytotoxic molecules that kill effector T-cells
  4. Metabolic disruption of inflammatory cells by competing for IL-2
151
Q

What steps need to be taken to generate therapeutic Tregs?

A
  1. Isolation of Tregs from patient blood (low numbers present)
  2. Expansion in vitro
152
Q

Which two methods for in vitro expansion of Tregs are there? What are their advantages?

A
  1. Polyclonal stimulation -> all Tregs expanded
  2. Antigen-specific stimulation -> stimulation of Tregs against desired antigens -> superior immunosuppressive properties
153
Q

What are the changes that have been introduced into the field of transplant medicine since the introduction of calcineurin inhibitors? (3)

A
  1. Low incidence of rejection
  2. Transplantation of other organs than kidney has become possible
  3. Allows for long graft and patient survival
154
Q

What are the disadvantages of calcineurin inhibitors? (4)

A
  1. Loss of kidney function
  2. (Lethal) side effects
  3. Not all allo-immunity sufficiently suppressed –> still chronic rejection
  4. Aspecific blocking of the whole immune system
155
Q

What is the mechanism of action of belatacept? What is the effect on T-cells? (4)

A

Blocking of CD80 & CD86, leading to:
1. No cell division
2. No cytokine production
3. Angergy
4. Apoptosis

156
Q

What are the advantages of belatacept vs. cyclosporine (=calcineurin inhibitor)? (2)

A
  1. Significantly better renal function
  2. 40% lower risk of death-censored graft failure
157
Q

What are the disadvantages of belatacept vs. cyclosporine? (3)

A
  1. Rejection significantly higher
  2. Risk of lymphoma increased
  3. More expensive
158
Q

What is the only situation in which belatacept is used over tacrolimus?

A

If a patient cannot tolerate tacrolimius

159
Q

What are the reasons why development of new immunosuppressive medication for transplantation medicine has slowed? (3)

A
  1. Newer drugs have not been proven beneficial over tacrolimus-MMF-steroids
  2. Emergence of generics of original drugs has lowered cost of maintenance immunosuppression
  3. Lack of acceptable/feasible clinical outcomes in research
160
Q

Which three mechanisms are still being investigated/introduced for targeting in transplantation medicine?

A
  1. IL-6 inhibitors
  2. Imlifidase
  3. CAR T-cells
161
Q

Which two anti-IL-6 drugs are currently being investigated for use in transplantation medicine? What is their mechanism of action?

A
  1. Tocilizumab -> blocks IL-6R
  2. Clazikizumab -> catches free IL-6
162
Q

Why is it advantageous to block IL-6 signaling in transplantation medicine?

A

IL-6 = inflammatory cytokine

163
Q

What is the mechanism of action of imlifidase?

A

Enzyme that cleaves IgG, allowing for removal of antibodies against graft

164
Q

What is the usecase of imlifidase in transplantation medicine?

A

Temporary removal of anti-graft antibodies gives a window for transplantation

165
Q

What are the disadvantages of imlifidase? (2)

A
  1. Antibodies are replaced over time
  2. Risk of infection during this period
166
Q

What is the promise of CAR T-cells in transplantation medicine?

A

Engineered CAR T-cell receptor to suppress immune responses against specific antigens (CAR Tregs)

I&I WC1 (20 decks)

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