Immunology: Immunosuppressants

Question 1

A patient is given a recombinant form of IL-2. Which 2 types of cancer can this recombinant drug be used to treat?

Answer 1

Renal cell carcinoma, metastatic melanoma (both treated with aldesleukin)

Question 2

Which 2 hematologic malignancies are glucocorticoids often used to treat?

Answer 2

Non-Hodgkin lymphoma and chronic lymphocytic leukemia

Question 3

A patient with Crohn disease who is receiving natalizumab therapy develops rapidly progressive paralysis and hyperreflexia. What virus is the probable culprit?

Answer 3

JC virus, which can cause progressive multifocal leukoencephalopathy (PML); the risk of PML is increased in patients treated with natalizumab

Question 4

Sirolimus (rapamycin) binds FKBP in the cell and subsequently inhibits what protein kinase?

Answer 4

mTOR (mechanistic target of rapamycin)

Question 5

A man taking allopurinol for gout starts taking an immunosuppressive agent for Crohn disease. Pancytopenia develops rapidly. What happened?

Answer 5

Azathioprine’s metabolite, 6-MP, is metabolized by xanthine oxidase; allopurinol inhibits xanthine oxidase, resulting in toxic levels of 6-MP

Question 6

Which 2 factors can amplify the nephrotoxicity of calcineurin inhibitors?

Answer 6

Administration at higher doses and poor baseline renal function

Question 7

A patient scheduled for kidney transplantation receives a monoclonal antibody against IL-2R for immunosuppression. Which side effects should be monitored?

Answer 7

Edema, hypertension, tremor (the prescribed drug is basiliximab)

Question 8

mTOR is responsible for driving the transcription of what types of genes?

Answer 8

Proliferation genes

Question 9

An elderly patient is diagnosed with CLL. What are the 2 molecular targets of the therapeutic antibodies commonly used to treat this disease?

Answer 9

CD-20 (targeted by rituximab) and CD52 (targeted by alemtuzumab); think “alymtuzumab” for chronic lymphocytic leukemia and “ri2Ximab” to target CD20

Question 10

6-Mercaptopurine (6-MP) inhibits what specific protein involved in nucleotide synthesis?

Answer 10

PRPP amidotransferase

Question 11

A patient develops severe hirsutism while taking cyclosporine for post-transplant immunosuppression. Which alternative drug with a similar mechanism of action may be ideal for her?

Answer 11

Tacrolimus (which does not cause the hirsutism or gingival hyperplasia associated with cyclosporine)

Question 12

What are the 2 main cancers that may be treated with trastuzumab?

Answer 12

Breast and gastric cancers (if positive for a HER2 mutation)

Question 13

Long-term use of immunosuppressants increases the risk of which 2 conditions?

Answer 13

Cancers and infections (immunosuppressants such as cyclosporine disrupt lymphocyte activation and growth)

Question 14

Apart from transplant rejection prophylaxis, what are the 3 main clinical indications for azathioprine?

Answer 14

Rheumatoid arthritis, glomerulonephritis, Crohn disease (and other autoimmune conditions)

Question 15

A patient is receiving long-term prednisone therapy for severe SLE. What are 2 potential effects of this medication on the bone?

Answer 15

Osteoporosis (predisposing to vertebral fracture), avascular/ischemic osteonecrosis (often of femoral head)

Question 16

Azathioprine inhibits proliferation of lymphocytes by blocking nucleotide synthesis. For which antimetabolite is azathioprine a precursor?

Answer 16

6-Mercaptopurine; “azathiopurine” interferes with nucleic acid synthesis (toxic to proliferating lymphocytes)

Question 17

With which 2 CD markers is the T-helper cell receptor associated?

Answer 17

CD3 and CD4

Question 18

Which 2 recombinant cytokines could be used to treat chemotherapy-induced leukopenia?

Answer 18

Filgrastim (G-CSF) and sargramostim (GM-CSF), which aid in the recovery of granulocyte and monocyte counts

Question 19

Which immunosuppressant medication is synergistic with cyclosporine?

Answer 19

Sirolimus (rapamycin); although cyclosporine can be used alone, sirolimus is not nephrotoxic (the kidney “sirvives”) and can enhance its efficacy

Question 20

A patient with NADPH oxidase deficiency has recurrent bacterial infections. What cytokine can be used to treat his condition?

Answer 20

IFN-γ (used to treat chronic granulomatous disease or CGD)

Question 21

What 3 types of cancer is bevacizumab commonly used to treat?

Answer 21

Renal cell carcinoma, non–small cell lung cancer, and colorectal cancer

Question 22

What recombinant antibody mimics the function of osteoprotegerin to prevent further bone loss in osteoporosis?

Answer 22

Denosumab (which, like osteoprotegerin, targets RANKL and inhibits osteoclast maturation)

Question 23

What is the molecular target of abciximab?

Answer 23

Abciximab targets platelet glycoproteins IIb/IIIa (ABC is as easy as 123), preventing platelet aggregation

Question 24

Both mycophenolate mofetil and azathioprine inhibit the de novo production of what type of nucleotides?

Answer 24

Purines (adenine, guanine)

Question 25

What are 3 clinical indications for treatment with interferon-α (IFN-α)?

Answer 25

Chronic hepatitis B, chronic hepatitis C (not preferred), renal cell carcinoma

Question 26

Which messenger, directly downstream from the T-cell receptor, is activated to promote inflammatory cytokine (eg, IL-2) gene transcription?

Answer 26

NFAT, which is generated from NFAT-P by calcineurin-mediated dephosphorylation (NFAT then enters the nucleus and promotes transcription)

Question 27

Apart from transplant rejection, what are the 2 main clinical indications for cyclosporine?

Answer 27

Psoriasis, rheumatoid arthritis

Question 28

A patient with psoriasis begins taking an immunosuppressant. After several months, she develops gingival hyperplasia and hirsutism. What drug is she taking?

Answer 28

Cyclosporine (tacrolimus has the same toxicity as cyclosporine but does not cause gingival hyperplasia or hirsutism)

Question 29

What is the primary molecular target inhibited by mycophenolate?

Answer 29

IMP dehydrogenase, which promotes purine synthesis

Question 30

A patient with optic neuritis and asymmetric neurologic deficits is treated with an antibody targeting α4-integrin. What immunosuppressive agent is she taking?

Answer 30

Natalizumab, which is used to treat multiple sclerosis (by targeting α4-integrin to impair leukocyte adhesion) is

Question 31

What is the mechanism of action of mycophenolate mofetil?

Answer 31

Mycophenolate mofetil reversibly inhibits IMP dehydrogenase, preventing purine synthesis in T and B cells

Question 32

A patient with severe persistent allergic asthma has frequent exacerbations despite high-dose inhaled steroid and long-acting β-agonist therapy. Which medication may be indicated?

Answer 32

Omalizumab, a recombinant antibody targeting IgE (used in treatment of refractory allergic asthma)

Question 33

Which 2 medications must bind FKBP to inhibit cellular immunity?

Answer 33

Tacrolimus and sirolimus

Question 34

A patient receiving a high maintenance dose of prednisone for several months runs out of her medication and cannot obtain a refill. For what complication is she at risk?

Answer 34

Adrenal insufficiency, which can develop as a result of abrupt steroid cessation (due to adrenal axis suppression in long-term steroid use)

Question 35

What is the mechanism of action of tacrolimus (FK506)?

Answer 35

FK506 binds to FK506 binding protein (FKBP) and inhibits calcineurin, thereby preventing IL-2 transcription and thus inhibiting T-cell activation

Question 36

Sirolimus (rapamycin) inhibits which target to exert its immunosuppressive effect?

Answer 36

mTOR

Question 37

Which 2 immunosuppressants are commonly associated with drug-induced kidney failure?

Answer 37

Cyclosporine and tacrolimus (calcineurin inhibitors)

Question 38

A patient presents with petechiae and is diagnosed with severe thrombocytopenia. Which 2 recombinant cytokines may be useful in treatment?

Answer 38

Romiplostim (thrombopoietin analog) and eltrombopag (thrombopoietin receptor agonist), which are platelet stimulators

Question 39

A patient presents with intermittently red urine and anemia. Flow cytometry shows deficient CD55 and CD59 on RBCs. What recombinant antibody may be used to treat this condition?

Answer 39

Eculizumab (used to treat paroxysmal nocturnal hemoglobinuria)

Question 40

A patient with an asthma exacerbation is treated with IV steroids. The next day, CBC shows a WBC count of 15,000. What is the mechanism behind this effect?

Answer 40

Glucocorticoids cause demargination of WBCs in the vasculature, producing an apparent (artificial) leukocytosis on blood testing

Question 41

How does the inhibition of NF-κB by steroids lead to immune system suppression?

Answer 41

NF-κB inhibition decreases cytokine transcription, suppressing B- and T-cell function while inducing T-cell apoptosis

Question 42

A premature infant has chronic lung disease. What is the target of the antibody that may be given to this infant to prevent RSV infection?

Answer 42

RSV F protein, which is targeted by palivizumab (paliVIzumab—VIrus) for RSV prophylaxis in high-risk infants

Question 43

What are 2 adverse effects that are more pronounced with use of tacrolimus compared with use of cyclosporine?

Answer 43

Diabetes (metabolic side effects) and neurotoxicity

Question 44

A patient experiences loss of vision and pain in her left eye. Brain MRI shows periventricular plaques. Which cytokine may be used in treatment?

Answer 44

IFN-β (often used to treat multiple sclerosis)

Question 45

Glucocorticoids inhibit the transcription of what types of genes?

Answer 45

Inflammatory cytokine genes

Question 46

A patient with high-risk unstable angina undergoes percutaneous coronary intervention. Which agent may be given to prevent additional ischemic complications?

Answer 46

Abciximab, an antiplatet agent targeting glycoproteins IIb/IIIa (ABC is as easy as 123)

Question 47

A patient presents with right-sided flank pain and hematuria. CT of the abdomen shows a complex renal mass. Which 2 recombinant cytokines can treat this condition?

Answer 47

Aldesleukin (recombinant IL-2) and IFN-α (interferon-α), both of which treat renal cell carcinoma

Question 48

Which immunosuppressant is often found in drug-eluting stents?

Answer 48

Sirolimus (rapamycin)

Question 49

A liver transplant recipient develops a buffalo hump, hyperglycemia, striae, and acne. Which drug class can cause such symptoms?

Answer 49

Glucocorticoids

Question 50

What are the 2 monoclonal antibodies that bind to and inhibit the IL-2 receptor (IL-2R)?

Answer 50

Daclizumab, basiliximab

Question 51

Which 2 recombinant antibodies are notorious for increasing the risk of PML in patients with latent JC virus infection?

Answer 51

Natalizumab and rituximab

Question 52

What are the 2 main indications for treatment with natalizumab?

Answer 52

Crohn disease and multiple sclerosis

Question 53

What molecule does the antibody omalizumab target?

Answer 53

IgE (thus preventing IgE from binding to FcεRI), useful in patients with refractory allergic asthma

Question 54

What are 3 benign ocular conditions that bevacizumab may be used to treat?

Answer 54

Macular edema, neovascular ("wet") age-related macular degeneration, and proliferative diabetic retinopathy

Question 55

A 65-year-old woman is found to have a T-score of -3.0 on a screening DEXA scan. Which therapeutic antibody would help to reduce her fracture risk?

Answer 55

Denosumab (denosumab helps make dense bones)

Question 56

Aldesleukin is a recombinant form of which cytokine?

Answer 56

Interleukin-2 (IL-2)

Question 57

A patient with end-stage renal disease presents with anemia and an MCV of 86 fL. What biologic agent can be used in treatment?

Answer 57

Epoetin alfa (an erythropoietin or EPO analog) which is useful in renal failure-associated anemias

Question 58

What are the 2 main indications for treatment with ustekinumab?

Answer 58

Psoriasis and psoriatic arthritis

Question 59

What is the mechanism of action of cyclosporine?

Answer 59

Cyclosporine inhibits calcineurin and binds cyclophilin, preventing IL-2 transcription and thus blocking T-cell activation

Question 60

Cyclosporine has several adverse effects. Which of these is most common and concerning?

Answer 60

Nephrotoxicity is most concerning (others include hypertension, hyperlipidemia, neurotoxicity, hirsutism, and gingival hyperplasia)

Question 61

What is the mechanism of action of sirolimus (rapamycin)?

Answer 61

Rapamycin inhibits mTOR, blocking T-cell activation and B-cell differentiation by inhibiting the cellular response to IL-2

Question 62

After "doing some reading" about rituximab therapy, a patient diagnosed with T-cell lymphoma asks you whether he would qualify for it. How do you respond?

Answer 62

Tell the patient he is not a candidate for this therapy, as rituximab targets CD20 on B cells (and is therefore used to treat B-cell non-Hodgkin lymphoma and CLL)

Question 63

Glucocorticoids inhibit what cellular protein complex implicated in DNA transcription and cytokine production?

Answer 63

NF-κB (nuclear factor κ-light chain enhancer of activated B cells)

Question 64

Which 2 immunosuppressants are specifically preferred for kidney transplant rejection prophylaxis?

Answer 64

Sirolimus and Basiliximab (think Sir Basil's kidney transplant)

Question 65

Which immunosuppressant may be specifically preferred for the treatment of lupus nephritis?

Answer 65

Mycophenolate mofetil

Question 66

A patient with Burkitt lymphoma is treated with a recombinant antibody targeting CD20. What is this agent?

Answer 66

Rituximab, which targets CD20 ("ri2Ximab") on B cells

Question 67

What 2 conditions may be treated with alemtuzumab?

Answer 67

CLL ("alymtuzumab" for chronic lymphocytic leukemia), multiple sclerosis (MS)

Question 68

What 2 recombinant antibodies have been developed to treat autoimmune diseases by targeting soluble TNF-α?

Answer 68

Infliximab and adalimumab

Question 69

A woman with progressive jaundice, ascites, and altered mental status tests positive for HBsAg and HBeAg. Which recombinant cytokine could help treat her condition?

Answer 69

Interferon-α (may be used in the treatment of chronic hepatitis B infection)

Question 70

A woman has breast cancer that is positive for a HER2 mutation. Which monoclonal antibody can be used in treatment?

Answer 70

Trastuzumab (HER2—"tras2zumab")

Question 71

What is the mechanism of action of basiliximab?

Answer 71

Basiliximab is a monoclonal antibody that blocks the IL-2 receptor

Question 72

What is the molecular target of eculizumab in the treatment of paroxysmal nocturnal hemoglobinuria (PNH)?

Answer 72

Complement protein C5

Question 73

What drug is a decoy TNF-α receptor that may be used to treat rheumatoid arthritis, IBD, psoriasis, and ankylosing spondylitis?

Answer 73

Etanercept (not a monoclonal antibody)

Question 74

What downstream messenger is activated by IL-2R signaling?

Answer 74

mTOR

Question 75

What are the 2 molecular targets of ustekinumab?

Answer 75

IL-12 and IL-23

Question 76

What are 2 key advantages associated with the use of mycophenolate mofetil for immunosuppression?

Answer 76

The drug is less nephrotoxic and less neurotoxic

Question 77

A patient presents with melena. Barium enema reveals an "apple core" sign. Colon cancer is diagnosed. Which recombinant antibody may be used in the therapy for this disease?

Answer 77

Bevacizumab, which targets VEGF to treat malignancies such as colorectal cancer

Question 78

What are 4 potential side effects of mycophenolate mofetil?

Answer 78

Hypertension, hyperglycemia, pancytopenia, gastrointestinal disturbance

Question 79

A man is diagnosed with age-related macular degeneration. Fundoscopic exam shows neovascularization. Using antibodies to inhibit which target may help?

Answer 79

VEGF (targeted by bevacizumab)

Question 80

What is the clinical advantage of combining different immunosuppressants?

Answer 80

Combining immunosuppressants increases their net efficacy while minimizing their individual toxicities

Question 81

A patient with lupus nephritis begins taking mycophenolate mofetil and subsequently develops an invasive viral infection. Which virus is the likely pathogen?

Answer 81

Cytomegalovirus (CMV); mycophenolate mofetil is associated with invasive CMV infection

Question 82

What is the molecular target of denosumab?

Answer 82

RANKL (like osteoprotegerin, denosumab inhibits osteoclast maturation by binding RANKL)

Question 83

Which 3 toxicities should a patient who is taking sirolimus (rapamycin) be warned about?

Answer 83

Pancytopenia, insulin resistance, hyperlipidemia (sirolimus causes "pansirtopenia")

Question 84

What 3 autoimmune conditions can rituximab be used to treat?

Answer 84

ITP, multiple sclerosis, and rheumatoid arthritis

Question 85

What are 4 clinical indications for treatment with adalimumab, infliximab, and etanercept?

Answer 85

Inflammatory bowel disease (Crohn disease or ulcerative colitis), rheumatoid arthritis, psoriasis, ankylosing spondylitis