Leukocyte Adhesion Deficiency

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

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 pus and/or 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
    • Assesses presence of beta 2 (β2) integrins CD11 and CD18
      • Decreased/absent expression of CD11/CD18 – consistent with leukocyte adhesion deficiency-1 (LAD1)
        • 2-10% expression – moderate deficiency; reasonable survival rate into adulthood
        • >10% expression – mild deficiency; may not be recognized until late teen years
        • <2% – severe deficiency; majority die in infancy unless bone marrow transplant is performed
      • Normal expression of CD11/CD18 – consistent with LAD2 or LAD3
    • Access presence of CD15 – indicated if LAD2 is suspected
      • Absent expression of CD15 – consistent with LAD2
    • Other testing 
      • Neutrophil rolling, neutrophil adherence, neutrophil motility – performed only in specialized laboratories
      • Bombay blood group phenotype testing – present in LAD2
      • Platelet aggregation – abnormal in LAD3
      • Molecular sequence analysis – to define exact molecular defect

Differential Diagnosis

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.

Epidemiology

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

Inheritance 

Pathophysiology

  • 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
    • Other LAD-like syndromes with defects in adhesion/chemotaxis have been identified (eg, RAC-2 which regulates actin cytoskeleton; leukocyte hyperadhesion syndrome)

Clinical Presentation

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.

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

Guidelines

Al-Herz W, Bousfiha A, Casanova J, Chatila T, Conley MEllen, Cunningham-Rundles C, Etzioni A, Franco JLuis, Gaspar B, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Picard C, Puck JM, Sullivan K, Tang ML K. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014; 5: 162. PubMed

General References

Etzioni A. Defects in the leukocyte adhesion cascade. Clin Rev Allergy Immunol. 2010; 38(1): 54-60. PubMed

Gazit Y, Mory A, Etzioni A, Frydman M, Scheuerman O, Gershoni-Baruch R, Garty B. Leukocyte adhesion deficiency type II: long-term follow-up and review of the literature. J Clin Immunol. 2010; 30(2): 308-13. PubMed

Harris ES, Smith TL, Springett GM, Weyrich AS, Zimmerman GA. Leukocyte adhesion deficiency-I variant syndrome (LAD-Iv, LAD-III): molecular characterization of the defect in an index family. Am J Hematol. 2012; 87(3): 311-3. PubMed

Immune Deficiency Foundation. Towson, MD [Accessed: Nov 2015]

Locke BA, Dasu T, Verbsky JW. Laboratory diagnosis of primary immunodeficiencies. Clin Rev Allergy Immunol. 2014; 46(2): 154-68. PubMed

Notarangelo LD, Badolato R. Leukocyte trafficking in primary immunodeficiencies. J Leukoc Biol. 2009; 85(3): 335-43. PubMed

Simpson BN, Hogg N, Svensson LM, McDowall A, Daley W, Yarbrough K, Abdul-Rahman OA. A new leukocyte hyperadhesion syndrome of delayed cord separation, skin infection, and nephrosis. Pediatrics. 2014; 133(1): e257-62. PubMed

Medical Reviewers

Last Update: August 2016