A 32-year-old man comes to the clinic for follow-up due to Crohn disease. The patient was initially diagnosed 3 years ago and achieved disease remission following a course of high-dose glucocorticoids. He remained in remission until 2 months ago, when he experienced an acute flare of diarrhea and abdominal pain that required a brief hospitalization and another course of high-dose glucocorticoids. The patient completed a prescribed glucocorticoid taper earlier this week and says that his symptoms have returned to "about normal." Azathioprine maintenance therapy is started to help prevent future flares. Which of the following most accurately describes the expected effects of this new medication on immune function?

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11ec160b_3b6f_64a9_9249_d5a35e81529c_MD0001_00 Azathioprine is an immunosuppression drug sometimes used in the treatment of autoimmune disease (eg, inflammatory bowel disease) and the prevention of organ transplant rejection. It generates 6-thioguanine metabolites that both inhibit an early step in de novo purine synthesis and act as false purine nucleotides that disrupt DNA and RNA replication. These effects are nonspecific and affect the proliferation of all rapidly dividing cells, including hematopoietic cells. Therefore, there is reduced proliferation of both B and T lymphocytes. The reduced number of activated T lymphocytes leads to reduced activity of IL-2, and the reduced number of activated B lymphocytes leads to reduced immunoglobulin levels. Common adverse effects of azathioprine include pancytopenia (ie, anemia, leukopenia, and thrombocytopenia) and increased susceptibility to infection. (Choice A) Rituximab is a monoclonal antibody sometimes used to treat autoimmune disease and hematologic malignancy. It binds to CD20 receptors on B lymphocytes, resulting in apoptosis; the B lymphocyte count and immunoglobulin levels are reduced, but there is minimal effect on T lymphocytes. (Choice C) Muromonab is a monoclonal antibody sometimes used to prevent organ transplant rejection. It binds to CD3 receptors on T cells to trigger apoptosis, reducing T-lymphocyte count and IL-2 activity. There is no direct effect on B lymphocytes, but B lymphocyte activity is reduced due to decreased activation by T lymphocytes. (Choices D and E) Azathioprine reduces the quantity and activity of both B and T lymphocytes. Immunoglobulin levels are usually directly related to B-lymphocyte count, and IL-2 activity is usually directly related to T-lymphocyte count; that is, if lymphocyte counts are low, immunoglobin levels and IL-2 activity are also low. Educational objective: Azathioprine is an immunosuppression drug that inhibits purine nucleotide synthesis and incorporates false purine nucleotides into DNA and RNA. These effects reduce the proliferation and activity of both B and T lymphocytes. __________ References: Azathioprine. (http://www.ncbi.nlm.nih.gov/pubmed/31194347)

A 32-Year-Old Man Comes to the Clinic for Follow-Up Due