A 3-year-old boy is being evaluated for persistent diarrhea. Although the patient seemed healthy at his 12-month well child visit, since then he has experienced 4 episodes of otitis media and 3 episodes of pneumococcal pneumonia. He was at the 50th percentile for weight and height at 12 months but is now at the 25th percentile for height and 10th percentile for weight. The patient is referred for upper gastrointestinal endoscopy, and Giardia lamblia is isolated from duodenal aspirates. Further workup shows very low serum levels of all immunoglobulin types. Flow cytometry of this patient's peripheral blood is most likely to show a near absence of cells bearing which of the following markers?

Question

A 3-year-old boy is being evaluated for persistent diarrhea.  Although the patient seemed healthy at his 12-month well child visit, since then he has experienced 4 episodes of otitis media and 3 episodes of pneumococcal pneumonia.  He was at the 50th percentile for weight and height at 12 months but is now at the 25th percentile for height and 10th percentile for weight.  The patient is referred for upper gastrointestinal endoscopy, and Giardia lamblia is isolated from duodenal aspirates.  Further workup shows very low serum levels of all immunoglobulin types.  Flow cytometry of this patient's peripheral blood is most likely to show a near absence of cells bearing which of the following markers?

Quizplus · Accepted Answer

This patient's recurrent sinopulmonary infections, Giardia lamblia gastroenteritis, failure to thrive, and low immunoglobulin levels are suggestive of X-linked agammaglobulinemia (XLA). In this condition, a mutation in the Bruton tyrosine kinase gene causes failure of bone marrow pre-B cells to develop into mature B cells, a step necessary for B cells to leave the bone marrow and enter the peripheral circulation. Patients with XLA have low or absent B cells in the peripheral blood and lymphoid tissues and pan-hypogammaglobulinemia (ie, very low IgG, IgM, and IgA). As a result, they are at increased risk of infection with pyogenic (encapsulated) bacteria. Patients also have increased susceptibility to certain viral and parasitic infections, such as enteroviruses and Giardia lamblia, due to the absence of opsonizing and neutralizing antibodies. Flow cytometry can be used to assess the number of circulating B cells by using fluorescent tags that bind to specific B cell surface proteins such as CD19, CD20, and CD21. (Choices A and B) CD4 is a helper T cell surface marker, and CD8 is a cytotoxic T cell surface marker. Both B cells and T cells can be deficient in patients with certain forms of severe combined immunodeficiency. However, these patients typically have failure to thrive, persistent mucosal candidiasis, and severe infections with opportunistic organisms (eg, Pneumocystis) at a much younger age (~6 months). (Choice C) CD15 is a cell surface protein present on granulocytes. It is also present on nearly all Reed-Sternberg cells and is therefore a cytologic marker useful in the diagnosis of Hodgkin lymphoma. (Choice D) CD16 is a low-affinity Fc receptor found on the surface of natural killer cells, neutrophils, and macrophages. Educational objective: X-linked agammaglobulinemia is characterized by low or absent circulating mature B cells (ie, CD19⁺, CD20⁺, CD21⁺ cells) and pan-hypogammaglobulinemia. Affected patients have increased susceptibility to pyogenic bacteria, enteroviruses, and Giardia lamblia due to the absence of opsonizing and neutralizing antibodies.

A 3-Year-Old Boy Is Being Evaluated for Persistent Diarrhea