Leukocyte Adhesion Deficiency


Indications for Testing

  • Child with delayed separation of the umbilical cord/or recurrent infections in whom more common immunodeficiencies have been ruled out
  • Tissue infections with absence of inflammatory cells and high peripheral neutrophil counts

Laboratory Testing

  • Initial screening
    • General immunodeficiency screening
      • CBC with differential
      • Comprehensive metabolic profile
      • Quantitative serum immunoglobulins (IgA, IgG, IgM)
      • Lymphocyte subset analyses – depending on clinical presentation
    • Rule out other diseases associated with immunodeficiency
      • HIV-1,2 testing
      • Plasma cell disorders – monoclonal protein detection, quantitation, and characterization with SPEP, IFE, IgA, IgG, IgM
      • Cystic fibrosis – sweat chloride testing using an accredited cystic fibrosis center
    • Rule out diseases associated with protein losses (eg, protein-losing enteropathy, nephropathy)
  • More specific screening – based on initial screening results
    • Clinical presentation may require multiple immune system investigations (see Immunodeficiency Evaluation algorithms)
    • Definitive diagnosis, prognostication, genetic counseling, and treatment may require genetic testing
    • Complement testing
  • Flow cytometric analysis
    • Assess presence of β2 integrins CD11 and CD18
      • Decreased/absent expression of CD11/CD18 – consistent with leukocyte adhesion deficiency-1 (LAD1)
        • 1-10% expression – 33% survive to age 40
        • >10% expression – mild deficiency; may not be recognized until late teen years
        • No expression – 75% die in infancy unless bone marrow transplant is performed
    • Access presence of CD15 – indicated if LAD2 is suspected
      • Absent expression of CD15 – consistent with LAD2
  • Other testing 
    • Neutrophil rolling, neutrophil adherence – performed only in specialized laboratories
    • Bombay blood group phenotype testing – for LAD2
    • Platelet aggregation – for LAD3
    • Sequence analysis – to define exact molecular defect

Differential Diagnosis

Clinical Background

Leukocyte adhesion deficiency disorders (LAD) are a primary immune deficiency syndromes that affect the leucocyte adhesion process. There are three types of LAD – 1, 2, and 3.  LAD1 is the most common type.


  • Incidence/prevalence – rare
    • LAD1 – most common type
  • Age – usually identified in infancy or early childhood


  • At least 3 types identified
    • LAD1
      • Autosomal recessive
      • Mutation of CD18 gene (ITGB2) – defect in expression of common chain (CD18) of β2 integrin family
    • LAD2
      • Autosomal recessive
      • Mutation of FUCT1 gene (GDP-fucose transporter 1) – defect in fucose metabolism leading to absence of sialyl-Lewis X (sLeX) ligand from phagocytes (CD15a)
    • LAD3
      • Autosomal recessive
      • Mutation of KINDLIN-3 gene – defect in inside-out signaling of β1, β2, and β3 integrins on leukocytes and platelets


  • LAD involves defects in integrin and selectin expression 
    • Blood neutrophils – the first line of defense against bacterial and fungal infection
    • Blood leukocytes migrate into the site of inflammation
      • Requires expression of P and E selectins on the endothelial cells with their ligands on leukocytes, which requires the family of integrins be present
        • CD18 – essential component of the β2 integrins (CD11a/CD18, CD11b/CD18, and CD11c/CD18)
    • Lack of integrin and selectin expression leads to defective adhesion of neutrophils that in turn leads to increased susceptibility to bacterial and fungal infections

Clinical Presentation

  • LAD1
    • Delayed separation of the umbilical cord
    • Recurrent soft tissue infections/ulcers
    • Chronic periodontitis
    • Marked leukocytosis and neutrophilia
    • Lack of neutrophils and no pus formation at sites of infection
  • LAD2 (very rare)
    • Same features as LAD1 (but no delay in separation of umbilical cord) plus
  • LAD3 (very rare)
    • Same features as LAD1
    • Bleeding tendency

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Initial testing to identify abnormalities in neutrophils

Leukocyte Adhesion Deficiency Panel 2004359
Method: Semi-Quantitative Flow Cytometry

Diagnosis of leukocyte adhesion deficiency

Panel includes CD11b, CD15, CD18

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Platelet Aggregation Studies 0030160
Method: Qualitative Aggregation