George Cunningham was diagnosed with Crohn's disease when 23 years old. He was experiencing acute abdominal pain, diarrhea, rectal bleeding, anemia and weight loss

Question

He did not respond to conventional immunosuppressive therapies and was given a course of infliximab, an anti-TNF-? monoclonal antibody that suppresses inflammation by blocking TNF-? activity. On day 12 after receiving his first infusion, he developed a mild fever, generalized vasculitis, swollen lymph glands, swollen joints and joint pain. Traces of blood and protein were detected in his urine. Which of the following is the most likely cause of these recent symptoms?
a. Type I hypersensitivity involving anaphylaxis.
b. Type II hypersensitivity leading to hemolytic anemia.
c. Type III hypersensitivity caused by immune complex deposition in blood vessels.
d. Type IV hypersensitivity involving CD8 T-cell cytotoxicity.
e. Type II hypersensitivity leading to thrombocytopenia.

Answer 1

Rationale: The correct answer is c. This is an example of serum sickness, a type III hypersensitivity reaction. George has made antibodies against infliximab, which is a chimeric monoclonal antibody made of human and mouse (foreign) components. Because this is an adaptive immune response, it takes time before sufficient levels of anti-infliximab antibody are made and cause the formation of immune complexes. Deposition of the immune complexes in blood vessels, joints, and glomeruli are causing George's symptoms. These symptoms are typically self-limiting, because as anti-infliximab antibody levels increase into the zone of antibody excess, the size of immune complexes will increase and they will then be cleared effectively by splenic macrophages, Kupffer cells of the liver, and mesangial cells of the kidney.