belatacept?
A. It is a fusion protein that binds CD80/CD86, preventing T-cell co-stimulation
B. It is a monoclonal antibody that binds CD3
C. It is a monoclonal antibody that binds CD25
D. It is a monoclonal antibody that binds CD20
CORRECT ANSWER: A. It is a fusion protein that binds CD80/CD86, preventing T-
cell co-stimulation
Rationale: Belatacept is a fusion protein consisting of the modified extracellular domain
of CTLA-4 linked to the Fc portion of human IgG1. It binds to CD80 and CD86 on
antigen-presenting cells with high a inity, preventing them from engaging CD28 on T
cells and thereby blocking the co-stimulatory signal required for full T-cell activation. It
is used for maintenance immunosuppression in renal transplantation. Adverse e ects
include post-transplant lymphoproliferative disorder (particularly in EBV-seronegative
patients) and increased risk of infection.
Question 2: Which of the following best describes the mechanism of action of
abatacept?
A. It is a fusion protein that binds CD80/CD86, preventing T-cell co-stimulation
B. It is a monoclonal antibody that binds CD3
C. It is a monoclonal antibody that binds CD25
D. It is a monoclonal antibody that binds CD20
CORRECT ANSWER: A. It is a fusion protein that binds CD80/CD86, preventing T-
cell co-stimulation
Rationale: Abatacept is a fusion protein consisting of the extracellular domain of CTLA-
4 linked to the Fc portion of human IgG1. It binds to CD80 and CD86 on antigen-
presenting cells, preventing them from engaging CD28 on T cells and thereby blocking T-
cell co-stimulation. It is used for rheumatoid arthritis and juvenile idiopathic arthritis.
Adverse e ects include increased risk of infection and infusion reactions.
Question 3: Which of the following structural di erences distinguishes belatacept
from abatacept?
A. Belatacept has two amino acid substitutions in the CTLA-4 domain that increase its
a inity for CD80/CD86
B. Belatacept is a monoclonal antibody, whereas abatacept is a fusion protein
C. Belatacept binds CD28, whereas abatacept binds CTLA-4
D. Belatacept is administered orally, whereas abatacept is administered intravenously
,CORRECT ANSWER: A. Belatacept has two amino acid substitutions in the CTLA-4
domain that increase its a inity for CD80/CD86
Rationale: Belatacept is a second-generation CTLA-4-Ig fusion protein with two amino
acid substitutions (L104E and A29Y) in the CTLA-4 domain that confer approximately
10-fold higher a inity for CD80/CD86 compared with abatacept. This increased avidity
makes belatacept suitable for maintenance immunosuppression in transplantation.
Abatacept is used primarily for autoimmune diseases. Both are fusion proteins, not
monoclonal antibodies.
Question 4: A renal transplant patient on belatacept develops post-transplant
lymphoproliferative disorder (PTLD). Which of the following risk factors is most
strongly associated with this complication?
A. EBV-seronegative recipient status
B. CMV-seropositive donor status
C. HLA mismatch
D. Male gender
CORRECT ANSWER: A. EBV-seronegative recipient status
Rationale: EBV-seronegative recipients receiving a kidney from an EBV-seropositive
donor are at highest risk for primary EBV infection and subsequent PTLD, particularly
when receiving belatacept. Belatacept impairs T-cell co-stimulation and reduces EBV-
specific T-cell immunity, increasing the risk of PTLD. EBV serostatus should be
determined before initiating belatacept, and the risk-benefit ratio should be carefully
considered in EBV-seronegative patients.
Question 5: Which of the following best describes the mechanism of action of
abatacept in rheumatoid arthritis?
A. It binds CD80/CD86 on antigen-presenting cells, preventing CD28-mediated co-
stimulation of T cells
B. It depletes B cells by binding CD20
C. It inhibits TNF-alpha
D. It inhibits JAK kinases
CORRECT ANSWER: A. It binds CD80/CD86 on antigen-presenting cells, preventing
CD28-mediated co-stimulation of T cells
Rationale: Abatacept binds CD80 and CD86 on antigen-presenting cells with high
a inity, preventing them from engaging CD28 on T cells. Without this co-stimulatory
signal, T-cell activation is impaired, reducing downstream inflammatory cytokine
production and autoantibody formation. It is used for rheumatoid arthritis and juvenile
idiopathic arthritis. Adverse e ects include increased risk of infection and infusion
reactions.
,Question 6: Which of the following best describes the mechanism of action of
alefacept?
A. It is a fusion protein that binds CD2, inhibiting T-cell activation
B. It is a monoclonal antibody that binds CD3
C. It is a monoclonal antibody that binds CD25
D. It is a monoclonal antibody that binds CD20
CORRECT ANSWER: A. It is a fusion protein that binds CD2, inhibiting T-cell
activation
Rationale: Alefacept is a fusion protein consisting of the extracellular domain of
lymphocyte function-associated antigen-3 (LFA-3) linked to the Fc portion of human
IgG1. It binds CD2 on T cells, blocking the LFA-3/CD2 interaction required for T-cell
activation. It was used for plaque psoriasis. It was withdrawn from the market due to
declining use and safety concerns.
Question 7: Which of the following best describes the mechanism of action of
etanercept?
A. It is a fusion protein that binds TNF-alpha and lymphotoxin-alpha
B. It is a monoclonal antibody that binds TNF-alpha
C. It is a monoclonal antibody that binds CD20
D. It is a fusion protein that binds CD80/CD86
CORRECT ANSWER: A. It is a fusion protein that binds TNF-alpha and lymphotoxin-
alpha
Rationale: Etanercept is a fusion protein consisting of the extracellular domain of the
human TNF receptor linked to the Fc portion of human IgG1. It binds to both TNF-alpha
and lymphotoxin-alpha (TNF-beta), neutralizing their activity. It is used for rheumatoid
arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis.
Unlike infliximab, it does not induce complement-mediated lysis of TNF-expressing
cells.
Question 8: Which of the following best describes the mechanism of action of
abatacept compared with belatacept?
A. Both are CTLA-4-Ig fusion proteins, but belatacept has higher a inity for CD80/CD86
B. Abatacept is a monoclonal antibody, whereas belatacept is a fusion protein
C. Abatacept binds CD28, whereas belatacept binds CTLA-4
D. Abatacept is used for transplantation, whereas belatacept is used for rheumatoid
arthritis
CORRECT ANSWER: A. Both are CTLA-4-Ig fusion proteins, but belatacept has
higher a inity for CD80/CD86
, Rationale: Both abatacept and belatacept are CTLA-4-Ig fusion proteins that bind
CD80/CD86 and block T-cell co-stimulation. Belatacept has two amino acid
substitutions (L104E and A29Y) that increase its a inity for CD80/CD86 approximately
10-fold compared with abatacept. Abatacept is used for autoimmune diseases
(rheumatoid arthritis, juvenile idiopathic arthritis), whereas belatacept is used for
maintenance immunosuppression in renal transplantation.
Question 9: A patient on belatacept for renal transplantation develops progressive
multifocal leukoencephalopathy (PML). Which of the following viruses is
responsible for this condition?
A. JC virus
B. BK virus
C. CMV
D. EBV
CORRECT ANSWER: A. JC virus
Rationale: Progressive multifocal leukoencephalopathy (PML) is caused by reactivation
of the JC virus (John Cunningham virus) in immunosuppressed patients. It presents with
progressive neurologic deficits, cognitive impairment, and motor weakness. Belatacept
and other immunosuppressants can increase the risk of PML by impairing T-cell-
mediated viral control. JC virus is a polyomavirus that remains latent in the kidneys and
lymphoid tissues after primary infection.
Question 10: Which of the following best describes the mechanism of action of
belatacept in preventing renal allograft rejection?
A. It blocks T-cell co-stimulation by binding CD80/CD86, preventing CD28 engagement
B. It depletes T cells by binding CD3
C. It inhibits calcineurin
D. It inhibits mTOR
CORRECT ANSWER: A. It blocks T-cell co-stimulation by binding CD80/CD86,
preventing CD28 engagement
Rationale: Belatacept binds CD80 and CD86 on antigen-presenting cells with high
a inity, preventing them from engaging CD28 on T cells. Without this co-stimulatory
signal, T-cell activation and proliferation are impaired, reducing the risk of allograft
rejection. It is used for maintenance immunosuppression in renal transplantation. It is
not a calcineurin inhibitor, mTOR inhibitor, or T-cell–depleting antibody.
Question 11: Which of the following best describes the mechanism of action of
abatacept in juvenile idiopathic arthritis?