CD18
Summary
CD18 is the beta-2 (β2) integrin subunit that pairs with various alpha subunits (CD11a, b, c) to form leukocyte adhesion molecules such as LFA-1 and Mac-1. Mutations in the ITGB2 gene encoding CD18 cause Leukocyte Adhesion Deficiency type 1 (LAD-1), impairing firm adhesion and transmigration of neutrophils to sites of infection.
Detail
CD18 (integrin β2 subunit) combines with CD11a, CD11b, or CD11c to form heterodimeric integrins: LFA-1 (CD11a/CD18), Mac-1/CR3 (CD11b/CD18), and p150,95 (CD11c/CD18). These integrins mediate firm adhesion of leukocytes to endothelial ICAM-1 during the leukocyte adhesion cascade (rolling → activation → firm adhesion → transmigration), critical for neutrophil recruitment to infection sites.
LAD-1 (Leukocyte Adhesion Deficiency type 1) results from autosomal recessive mutations in ITGB2, causing absent or dysfunctional CD18 protein. This leads to defective firm adhesion and diapedesis of neutrophils, despite normal or elevated circulating neutrophil counts (due to failure to marginate/adhere and exit the vasculature).
Clinical features of LAD-1 (classic USMLE association): - Recurrent bacterial and fungal infections without pus formation (neutrophils can't extravasate) - Delayed separation of the umbilical cord (>3 weeks) - Impaired wound healing - Persistent leukocytosis (neutrophilia) due to failure of neutrophils to leave the bloodstream - Absence of pus at infection sites despite significant infection burden
Severity correlates with the degree of CD18 deficiency: severe phenotype (<1% expression) vs. moderate phenotype (1-30% expression). Diagnosis often made via flow cytometry showing absent/decreased CD18 expression on leukocytes. Treatment includes aggressive infection management, and in severe cases, hematopoietic stem cell transplantation.
High-yield distinction: LAD-1 (CD18 defect) vs. LAD-2 (defect in fucosylation affecting selectin ligands, causing rolling defect) - LAD-1 is far more commonly tested.
Sources
- First Aid for the USMLE Step 1
- Robbins Basic Pathology
- Kumar & Clark's Clinical Medicine
- Janeway's Immunobiology
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