A patient with recurrent severe bacterial infections is found to have a hereditary deficiency of leukocyte adhesion molecule CD18. He shows a markedly elevated peripheral neutrophil count but poor wound healing and absent pus formation. Which adhesion step is primarily impaired?
- A Leukocyte rolling on endothelium
- B Chemotaxis toward the site of infection
- C Firm adhesion of leukocytes to endothelium and transmigration ✓
- D Opsonin-independent phagocytosis of bacteria
Explanation
Leukocyte adhesion deficiency (LAD) type I results from mutations in the CD18 subunit shared by beta-2 integrins (LFA-1/CD11a/CD18, MAC-1/CD11b/CD18, and p150,95). Loss of beta-2 integrins prevents firm adhesion to ICAM-1/ICAM-2 on endothelium and subsequent transmigration, so neutrophils cannot leave blood vessels to enter tissues. Rolling via selectins is intact (explaining leukocytosis from marginating pool release), but no pus forms because neutrophils cannot extravasate. Chemotaxis and phagocytosis would also be impaired secondarily but the primary step affected is firm adhesion.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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