Christiana Carter had no obvious problems until she was 18 months old, when she stopped gaining weight, her appetite became poor, and she had recurrent episodes of diarrhea

Question

At 24 months, Christiana developed a cough with pulmonary infiltrates unresponsive to treatment with the antibiotics clarithromycin and trimethoprim/sulfamethoxazole. Within 3 months, she developed lymphadenopathy, hepatosplenomegaly, and fevers. A computed tomography scan revealed enlarged mesenteric and para-aortic lymph nodes. A biopsy of an enlarged axillary lymph node revealed acid-fast bacilli, and cultures from the lymph node and blood grew Mycobacterium fortuitum. HIV was ruled out after negative tests by ELISA and PCR. Serologic testing for tetanus antitoxoid antibody showed a normal post-vaccination level. Christiana's peripheral blood mononuclear cells (PBMCs) were cultured with interferon-? plus lipopolysaccharide with no significant increase in TNF-? production. A variety of broad-spectrum and anti-mycobacterial antibiotics were administered, lowering the fever, and over the course of the next 2 months Christiana began to gain weight but continued to show signs of persistent infection. Which of the following is the most likely explanation for these clinical findings?
a. leukocyte adhesion deficiency
b. chronic granulomatous disease
c. interferon-? receptor deficiency
d. X-linked agammaglobulinemia
e. severe combined immune deficiency.

Answer 1

Rationale: The correct answer is c. The key finding here is the unresponsiveness of Christiana's PBMCs to interferon-γ (IFN-γ) plus LPS. When IFNγ binds the IFNγ receptors of macrophages, these cells become stimulated and very effective at killing intravesicular bacteria such as mycobacteria. Defects in the IFN-γ a receptor are associated with persistent mycobacterial infections. Because of Christiana's age, she is likely to be homozygous for a recessive mutation in IFNγR1 that leads to the lack of receptor. Chronic granulomatous disease and leukocyte adhesion disease result from defects in NADPH oxidase and CD18, respectively, but these defects would not hinder the ability of PBMCs from affected individuals to produce TNF-α in response to IFN-γ. Because Christiana has normal levels of tetanus antitoxoid antibody, she does not have X-linked agammaglobulinemia or severe combined immune deficiency.