Leukocyte Adhesion Deficiency

Pathophysiology And Classification

Leukocyte Adhesion Deficiency represents a specific disorder of phagocyte adhesion.
Affected neutrophils possess normal killing capabilities but cannot firmly adhere to endothelial intercellular adhesion molecules (ICAM-1 and ICAM-2).
Neutrophils also fail to recognize iC3b-opsonized microbes.
This failure completely prevents the transmigration of neutrophils into tissues and halts subsequent phagocytosis.

Subtype	Genetic Defect	Immunologic Mechanism	Distinctive Clinical Features
LAD Type 1	Autosomal recessive defect in the ITGB2 gene.	Absence or severe reduction of the CD18 subunit of $β_{2}$ -integrins.	Classic severe infections lacking pus formation.
LAD Type 2	Defect in the fucose transporter.	Absence of sialyl Lewis X, which prevents selectin-mediated rolling.	Milder infections, intellectual disability, and the Bombay blood phenotype.
LAD Type 3	Pathogenic variants in the FERMT3 gene (Kindlin-3).	Defective integrin activation.	Infectious features of LAD-1 combined with a severe Glanzmann thrombasthenia-like bleeding disorder.

LAD type 1 classically presents in the neonatal period.
Delayed separation of the umbilical cord is a defining early sign.
This delayed separation is typically accompanied by severe omphalitis.
Patients develop recurrent bacterial infections of the skin and mucosal surfaces.
Skin infections rapidly progress to large, chronic, and indolent ulcers.
These ulcers heal very slowly and frequently require plastic surgery grafting.

Severe necrotizing gingivitis and periodontitis are prominent features.
These dental complications lead to the premature loss of both primary and secondary teeth.
A hallmark clinical paradox is the complete absence of pus formation.
There is a striking lack of neutrophilic infiltration at sites of active, severe infection.

A complete blood count reveals extreme, persistent neutrophilic leukocytosis.
Neutrophil counts frequently exceed 25,000/µL and often surpass 100,000/µL during active infections.
This marked leukocytosis occurs notably alongside periods without obvious pus formation.

The diagnosis is definitively established by utilizing flow cytometry to evaluate specific surface adhesive glycoproteins.
Diagnosis of LAD type 1 requires demonstrating the absence or severe reduction of CD11b and CD18 ( $β_{2}$ -integrins) on the surface of neutrophils.
Diagnosis of LAD type 2 is established by demonstrating the absence of the sialyl Lewis X antigen (CD15) on neutrophils.

Patients require continuous, targeted antibiotic prophylaxis.
Antibiotic regimens are specifically designed to protect against Staphylococcus aureus and gram-negative bacilli.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the definitive and potentially curative treatment for LAD.
Early HSCT is strongly recommended for patients with severe LAD-1.