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Leukocyte adhesion deficiency

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Leukocyte adhesion deficiency

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Leukocyte adhesion deficiency

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USMLE® Step 1 style questions USMLE

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A 16-month old girl comes to the office because of severe abdominal pain for 2 days. Her mother says that she has been febrile and vomiting. Medical history includes 5 cases of omphalitis (infection of the umbilical cord stump) and 2 cases of pneumonia. Examination shows a very tender abdomen with rebound tenderness. Her CBC is as follows: WBC 80,000/mm3, lymphocytes: 23%, neutrophils: 67 %, Monocytes: 4%, Eosinophils: 4%, Hb: 11 g/dL, Platelets: 375,000/mm3. Which of the following is the most likely diagnosis?

Transcript

Content Reviewers:

Rishi Desai, MD, MPH

Leukocyte adhesion deficiency is a rare inherited immunodeficiency which develops because a group of immune cells called phagocytes fail to bind to the blood vessel wall, and therefore cannot get to the site of inflammation or tissue injury.

Normally, phagocytes, which are mostly neutrophils, circulate in the blood waiting for a signal that something’s wrong somewhere in the body.

As soon as this signal comes, in the form of cytokines which are pro-inflammatory molecules, they try to speed over to the affected tissue.

But to get there, they first have to pass through the endothelial cells that line the blood vessel wall.

Getting through the endothelial cells is known as extravasation and involves multiple steps.

First, the endothelium expresses molecules called selectins, which binds to sialyl-Lewis X, a carbohydrate that’s found on the surface of phagocytes, making them slow down and roll along the vessel wall.

Second, is a step called adhesion.

That’s basically a tight interaction between cellular adhesion molecules on the surface of endothelial cells, and integrins on the surface of the phagocytes.

Third, phagocytes manage to transmigrate or squeeze around the endothelial junctions, which are the sites of connection between two adjacent endothelial cells.

Fourth, the phagocytes use the concentration gradient of the cytokine signals to move towards the area of inflammation.

This process is critical for destroying invading pathogens, in particular bacteria and fungi.

In fact, after a long battle with bacterial or fungal cells, phagocytes, especially neutrophils, die and can form a collection of pus, which can accumulate in a closed tissue space, developing into an abscess.

The process of extravasation is also essential for wound healing, where phagocytes help remove dead and damaged cells.

In addition to typical settings of wound healing, this function of phagocytes is required soon after birth.

That’s because once the umbilical cord is cut, the cells within the cord being to die, and these dead cells are engulfed by phagocytes.

That process helps the dry umbilical cord separate from the baby’s abdomen.

In leukocyte adhesion deficiency, there’s a mutation in a gene that encodes some of the molecules that mediate the interaction between phagocytes and endothelial cells.

There are two major types, based on the step that’s affected.

Leukocyte adhesion deficiency type I is by far the most common and results from a failure to express CD18, which is a subunit of integrin molecules.