Review Question - QID 215191

This patient who had delayed separation of the umbilical cord and later presents with recurrent mucosal and soft tissue infections most likely has leukocyte adhesion deficiency. This disease is caused by a defect in the translocation of neutrophils through the vascular endothelium at sites of inflammation.

Leukocyte adhesion deficiency is a primary immunodeficiency resulting from phagocytic dysfunction. It is inherited in an autosomal recessive manner and is caused by a defect in the lymphocyte function-associated antigen 1 (LFA-1) integrin protein on leukocytes (also known as cluster of differentiation 18, or CD18). This protein normally promotes adhesion of inflammatory cells to the vascular endothelium at sites of inflammation so that they can translocate through the basement membrane into the affected tissue. A defect in this process will therefore result in an inability to respond effectively to superficial skin, soft tissue, and mucosal infections. A pathognomonic characteristic of this disease is delayed separation of the umbilical cord past 30 days of life.

Illustration A demonstrates how integrins allow for translocation of immune cells through the vascular endothelium. This process is defective in leukocyte adhesion deficiency.

Incorrect Answers:
Answer 2: Creation of superoxide free radicals is defective in patients with chronic granulomatous disease. These patients will present with recurrent pyogenic infections with catalase-positive organisms. Patients may also have eczematoid dermatitis.

Answer 3: Differentiation of T-cells is defective in patients with hyper IgE syndrome (Job syndrome). These patients will present with coarse facies, cold staphylococcal abscesses, retained primary teeth, and dermatologic problems.

Answer 4: Formation of phagolysosomes is defective in patients with Chediak-Higashi syndrome. These patients will present with hypopigmentation of skin, eyes, and hair as well as pancytopenia.

Answer 5: Immunoglobulin class switching is defective in patients with hyper IgM syndrome. These patients will present with severe pyogenic infections early in life, chronic diarrhea, and opportunistic infections such as Pneumocystis, Cryptosporidium, cytomegalovirus, and echovirus encephalitis.

Bullet Summary:
Leukocyte adhesion deficiency is caused by defective integrins resulting in the inability of neutrophils to bind and translocate through the vascular endothelium.