2. A 27-year-old woman develops oliguria 10 days after an uncomplicated kidney transplant. Evaluation includes a kidney biopsy that demonstrates a lymphocytic infiltrate in the tubular interstitium. Because she does not respond to steroid boluses over several days, a repeat biopsy is performed. OKT3 therapy is started for steroid resistant rejection. That afternoon, the patient develops severe rigors, a temperature of 39.3°C, a blood pressure of 89/64 mm Hg, and shortness of breath. Which one of the following is the most likely
explanation for these findings?
(A) Fluid overload due to renal insufficiency (B) Treatment with OKT3
(C) Cytomegalovirus viremia (D) Renal graft rejection
(E) Pneumocystis carinii pneumonia
2–B. Cytokine release syndrome from treatment with OKT3 is the most likely explanation for the findings described. The binding of OKT3 to
CD3 antigens on T cells leads to the release of cytokines, resulting in symptoms similar to this patient's. Cytokine release syndrome is associated most commonly with the first dose. Pretreating with diphenhydramine, acetaminophen, steroids, and narcotics can reduce the symptoms. Fluid overload is not commonly associated with fevers and rigors. Cytomegalovirus and Pneumocystis carinii pneumonia do not commonly occur within the first month after transplantation. Allograft rejection itself is associated with fever but would be less likely to explain the other symptoms.
3. During cardiac transplantation, a recipient requires multiple blood transfusions from blood loss during surgery. During the operation, the patient develops sudden hypotension, bleeding from intravenous sites and wound edges, along with severe tachycardia. Which of the following is the most likely cause of these findings?
(A) Type I immediate hypersensitivity (B) Type II cytotoxic hypersensitivity (C) Previous aspirin therapy
(D) Type IV delayed hypersensitivity (E) Previous warfarin therapy
3–B. Blood transfusion reaction—a type II cytotoxic hypersensitivity—commonly is associated with hypotension, tachycardia, and diffuse
bleeding in an anesthetized patient. This reaction occurs when preformed antibodies to transfused red blood cell antigens are present in the recipient, leading to complement mediated lysis. Type I reactions are mediated by immunoglobulin (Ig)E to allergen, leading to mast cell or basophil degranulation. Previous aspirin or warfarin therapy would likely be associated with persistent bleeding throughout the
operation and would not lead to sudden hypotension. Type IV sensitivity occurs 48–72 hours after exposure to antigen and is associated with sensitized helper T cells.
4. After an uncomplicated renal transplantation, a patient inadvertently removes his Foley catheter on the first postoperative day. Why should the Foley catheter be reinserted?
(A) Hourly urine output monitoring is necessary.
(B) Foley catheters decrease the risk of urinary tract infections (UTI). (C) Foley catheters decompress the bladder.
(D) Urethral strictures occur more commonly after kidney transplantation. (E) Use of Foley catheters prevents acute rejection.
4–C. After ureteroneocystostomy, decompression of the bladder for several days using a Foley catheter allows healing of the anastomosis.
Urine output monitoring aids in detection of renal hypoperfusion and graft rejection but can be accurately measured in this setting without the use of a Foley catheter. Foley catheters are associated with an increased rate of urinary tract infections. Overdistension of the bladder can lead to breakdown of the anastomosis of the ureter to the bladder. Although ureter strictures are not uncommon after renal transplantation, urethral strictures are rare. Foley catheters do not prevent rejection.
5. A 49-year-old woman develops markedly increased liver enzymes on the ninth postoperative day after liver transplantation for hepatitis C. Further evaluation includes a Doppler ultrasound demonstrating adequate hepatic blood flow, and liver biopsy demonstrating endothelialitis and bile duct damage. Which of the following therapies is most likely to be effective?
(A) Interferon therapy for recurrent hepatitis C (B) Steroid bolus therapy for rejection
(C) Reoperation for portal vein thrombosis (D) Reoperation for bile duct stricture (E) Observation with repeat biopsy in 1 week
5–B. The pathologic findings and time course described are consistent with acute cellular rejection. M ore than half of liver transplant
recipients will develop acute rejection, most within the first 4 weeks. Initial therapy often includes steroid boluses. Hepatitis C, like many other indications for transplantation, may recur 3–6 months after transplantation. Adequate hepatic blood flow on Doppler ultrasound decreases the likelihood of portal vein thrombosis. Bile duct strictures are often associated with jaundice and characteristic pathologic findings. Observation alone may lead to graft loss due to rejection.
6. A 59-year-old man with chronic renal insufficiency presents for repeat kidney transplantation after loss of a previous graft. After the arterial and venous anastomosis are complete, the vascular clamps are removed and excellent perfusion of the kidney is observed. Thirty minutes later, the kidney is noted to have a bluish discoloration, loss of perfusion, and lack of urine production. Which of the following statements is true regarding this patient?
(A) This is due to class II HLA antibodies.
(B) A similar reaction is the major barrier to xenotransplantation. (C) This reaction cannot be avoided.
(E) Emergent treatment with OKT3 is indicated.
6–B. The development of a bluish discoloration, and loss of perfusion and function within minutes to hours after revascularization is rare,
but often due to hyperacute rejection. Hyperacute rejection occurs when preformed recipient antibodies act against class I donor antigens. Humans have preformed antibodies to animal antigens, making hyperacute rejection the major barrier to xenotransplantation. This reaction can almost always be avoided by performing a crossmatch. This assay is performed by adding donor serum to recipient lymphocytes in the presence of complement. If preformed antibodies are in the donor serum, cell lysis will occur. Although liver allografts are relatively resistant to hyperacute rejection, heart, pancreas, lung, and kidney are susceptible. Hyperacute rejection is refractory to therapy and almost always results in loss of the graft. OKT3 is indicated in the setting of acute rejection but has less of a role in
hyperacute rejection.
7. An 18-year-old woman with cystic fibrosis underwent bilateral lung transplantation 15 months ago. She now presents with a dry cough, and dyspnea refractory to bronchodilators. She has been observed to have a serial decline in her forced expiratory volume (FEV) over the past 3 months. Transbronchial lung biopsy is consistent with obliterative bronchiolitis (OB). Which of the following statements is true?
(A) No satisfactory treatment for reversal of this condition currently exists. (B) The fibrosis can be reversed with increased immunosuppression. (C) M ost patients stop progressing with adequate therapy.
(D) OB occurs in less than 5% of all lung transplants. (E) OB is a manifestation of acute rejection.
7–A. Obliterative bronchiolitis (OB) has become recognized as the main impediment to long-term survival after lung transplantation. At
present, no satisfactory therapy can reverse the fibrosis once it occurs. Although current treatment often involves increased
immunosuppression, most patients continue to have progression of disease. OB occurs in ~ 50% of lung transplant recipients and is believed to be a manifestation of chronic rejection.
Directions: Each set of matching questions in this section consists of a list of four to twenty-six lettered options followed by several
numbered items. For each numbered item, select the appropriate lettered option(s). Each lettered option may be selected once, more than once, or not at all.
Questions 8-10
A. Cyclosporine
B. M ycophenolate mofetil C. OKT3
D. Cyclophosphamide
E. Antithymocyte globulin (ATG) F. Azathioprine
G. Tacrolimus H. Glucocorticoids
M atch each immunologic drug with the most likely associated description.
8. A 49-year-old man with steroid resistant rejection of a renal allograft develops high fever, tachycardia, and shortness of breath 30 minutes after administration of this medication. (SELECT 1 DRUG)
8-C. OKT3 is a monoclonal antibody directed against the CD3 complex commonly used for induction therapy and treatment of steroid
resistant rejection. Binding of OKT3 to the CD3 complex induces the release of multiple cytokines, and is associated with fever, chills, wheezing, pulmonary edema, tachycardia, hypotension, and rarely, death. This occurs most commonly within 30 minutes to 4 hours after the first dose and usually subsides with subsequent doses.
9. Patients receiving this agent specifically have significantly decreased production of interleukin (IL)-2. (SELECT 2 DRUGS)
9-A and G. Cyclosporine and tacrolimus both function by decreasing the release of interleukin (IL)-2. Cyclosporine is useful for induction
and maintenance therapy but has no benefit in treating rejection. In contrast, tacrolimus can be used for resistant rejection and “rescue therapy” of grafts failing on cyclosporine.
10. When used in transplant recipients, this agent specifically binds to multiple cell surface receptors on the T cell. (SELECT 1 DRUG) 10-E. Antithymocyte globulin (ATG) and antilymphocyte globulin are polyclonal antibodies directed against T cell antigens including CD2,
CD3, CD4, and CD8, as well as B cell, platelet, monocyte, and granulocyte antigens. OKT3 is a monoclonal antibody directed against the CD3 antigen of T cells. These three agents are used for induction therapy as well as treatment of resistant or severe rejection.