Leukocyte Adhesion Deficiency Type 1, CD11a/CD18 and CD11b/CD18 Complex Immunophenotyping, Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Leukocyte adhesion deficiency syndrome type 1 (LAD-1) is an autosomal recessive disorder caused by mutations in the common chain (CD18) of the beta2-integrin family. LAD-1 is clinically characterized by recurrent infections, impaired wound healing, delayed umbilical cord separation, persistent leukocytosis, and recurrent soft tissue and oral infections.
Each of the beta2-integrins is a heterodimer composed of an alpha chain (CD11a, CD11b, or CD11c) noncovalently linked to a common beta2-subunit (CD18). The alpha-beta heterodimers of the beta2-integrin family include LFA-1 (CD11a/CD18), Mac-1/CR3 (CD11b/CD18), and p150/95 (CD11c/CD18).(1-4) The CD18 gene, ITGB2, and its product are required for normal expression of the alpha-beta heterodimers. Therefore, defects in CD18 expression lead to either very low or no surface membrane expression of CD11a, CD11b, and CD11c.
Severe and moderate forms of LAD-1 exist, differing in the degrees of protein deficiency, which are caused by different ITGB2 mutations. Two relatively distinct clinical phenotypes of LAD-1 have been described. Patients with the severe phenotype (<1% of normal expression of CD18 on neutrophils) characteristically have delayed umbilical stump separation (>30 days), infection of the umbilical stump (omphalitis), persistent leukocytosis (>15,000/microliter) in the absence of overt active infection, and severe destructive gingivitis with periodontitis and associated tooth loss, and alveolar bone resorption. Patients with the moderate phenotype of LAD-1 (1%-30% of normal expression of CD18 on neutrophils) tend to be diagnosed later in life. Normal umbilical separation, lower risk of life-threatening infections, and longer life expectancy are common in these patients. However, leukocytosis, periodontal disease, and delayed wound healing are still very significant clinical features.
Patients with LAD-1 (and other primary immunodeficiency diseases) are unlikely to remain undiagnosed in adulthood. Consequently, this test should not be typically ordered in adults for LAD-1. However, it may be also used to assess immune competence by determining CD18, 11a, and 11b expression.
Aids in the diagnosis of leukocyte adhesion deficiency syndrome type 1, primarily in patients younger than 18 years of age
CD11a, CD11b, and CD18 phenotyping
The report will include a summary interpretation of the presence or reduction in the level of expression of the individual markers (CD11a, CD11b, and CD18). Expression of the individual markers provides indirect information on the presence or absence of the CD11a/CD18 and CD11b/CD18 complexes.
Specimens obtained from patients with leukocyte adhesion deficiency syndrome type 1 (LAD-1) show significant reduction (moderate phenotype) or near absence (severe phenotype) of CD18 and its associated molecules, CD11a and CD11b, on neutrophils and other leukocytes.
CD11c expression also is low in LAD-1. The analytical sensitivity of the CD11c assay is insufficient to allow interpretation of CD11c surface expression. Therefore, we test only for expression of CD18, CD11a, and CD11b.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is typically not indicated in adults. For questions about appropriate test selection, contact Mayo Medical Laboratories.
Patients with normal beta2-integrin expression without functional activity have been described.(5-6) Therefore, expression of CD18 alone is insufficient to exclude the diagnosis of leukocyte adhesion deficiency syndrome type 1 (LAD-1); functional assays (eg, neutrophil chemotaxis, random migration assays) must be performed if the clinical suspicion is high.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Normal (reported as normal or absent expression for each marker)
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Anderson DC, Springer TA: Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Ann Rev Med 1987;38:175-194
2. Corbi AL, Vara A, Ursa A, et al: Molecular basis for a severe case of leukocyte adhesion deficiency. Eur J Immunol 1992;22:1877-1881
3. Harlan JM: Leukocyte adhesion deficiency syndrome: insights into the molecular basis of leukocyte emigration. Clin Immunol Immunopathol 1993;67:S16-S24
4. O'Gorman MR, McNally AC, Anderson DC, et al: A rapid whole blood lysis technique for the diagnosis of moderate or severe leukocyte adhesion deficiency (LAD). Ann NY Acad Sci 1993;677:427-430
5. Hogg N, Stewart MP, Scarth SL, et al: A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest 1999;103:97-106
6. Kuijpers TW, van Lier RAW, Hamann D, et al: Leukocyte adhesion deficiency type 1 (LAD/1) variant. J Clin Invest 1997;100:1725-1733