Hematologically important mutations: Leukocyte adhesion deficiency (second update).

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Leukocyte adhesion deficiency (LAD) is a group of primary immunodeficiencies characterized by impaired leukocyte adhesion.
• This defect leads to recurrent severe bacterial infections, neutrophilia, and poor wound healing.

Purpose of the Study:

• To provide an updated overview of the genetic mutations associated with different forms of LAD.
• To highlight the molecular mechanisms underlying leukocyte dysfunction in LAD.

Main Methods:

• Review of genetic databases and literature.
• Analysis of mutations in genes encoding key adhesion molecules and regulatory proteins.

Main Results:

• LAD-I is caused by mutations in ITGB2 (CD18), affecting β2 integrins.
• LAD-II results from mutations in SLC35C1, impacting fucosylation and selectin ligand formation.
• LAD-III is linked to FERMT3 mutations, disrupting β integrin activation and causing leukocyte/platelet dysfunction.

Conclusions:

• Genetic defects in leukocyte adhesion molecules and their regulators lead to distinct LAD subtypes.
• Understanding these mutations is crucial for diagnosis and potential therapeutic strategies.