Leukocyte adhesion deficiency

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Leukocyte-adhesion deficiency
Classification and external resources
OMIM 116920
eMedicine ped/1302
MeSH D018370

Leukocyte adhesion deficiency (LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections.[1] LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a Glanzmann thrombasthenia-like bleeding tendency.[2][3]

Characteristics[edit]

LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing. The defects adhesion result in poor leukocyte chemotaxis, particularly neutrophil, inability to form pus and neutrophilia.[3]

Individuals with LAD suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, and peritonitis are common and often life-threatening due to the infant's inability to properly destroy the invading pathogens. These individuals do not form abscesses because granulocytes cannot migrate to the sites of infection.

Cause and genetics[edit]

Leukocyte-adhesion deficiency has an autosomal recessive pattern of inheritance.

Types include:

Type OMIM Gene
LAD1 116920 ITGB2
LAD2 or CDG2C 266265 SLC35C1
LAD3 612840 FERMT3

The most common type is LAD1.

The inherited molecular defect in patients with LAD1 is a deficiency of the β-2 integrin subunit,[4] also called CD18, of the leukocyte cell adhesion molecule, which is found on chromosome 21. This subunit is involved in making three other proteins (LFA-1, Integrin alphaXbeta2, and Mac-1/CR3). This basically means the gene creates a nonfunctioning protein, which results in the lack of LFA1 integrin, which allows neutrophils to make their way out of the blood stream by adhering to the Ig family receptor ICAM on the apical surface of endothelial cells in the infected areas of the body (i.e. the lungs in pneumonia). The bacteria can then proliferate, leading to symptomatic infection. The infection can spread unimpeded and cause serious injury to important tissue.

Diagnosis[edit]

Typically, diagnosis is made after several preliminary tests of immune function are made, including basic evaluation of the humoral immune system and the cell-mediated immune system. A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels. Specific diagnosis is made through monoclonal antibody testing for CR3, one of the three complete proteins which fail to form properly as a result of β-2 integrin subunit deficiency.

Treatment[edit]

Once the diagnosis of LAD is made, bone marrow transplantation is the current standard of care.[5] However, some progress has been made in gene therapy, an active area of research.

Epidemiology[edit]

LAD is a rare disease, with an estimated prevalence of one in 100,000 births, with no described racial or ethnic predilection.

See also[edit]

External links[edit]

References[edit]

  1. ^ "Leukocyte Adhesion Deficiency: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01. 
  2. ^ Robert P, Canault M, Farnarier C, Nurden A, Grosdidier C, Barlogis V, … Alessi MC (2011). "A novel leukocyte adhesion deficiency III variant: kindlin-3 deficiency results in integrin- and nonintegrin-related defects in different steps of leukocyte adhesion". Journal of Immunology 186 (9): 5273–83. doi:10.4049/jimmunol.1003141. PMID 21441448. 
  3. ^ a b Abbas AK, Lichtman AH, Pillai S (2012). Cellular and molecular immunology (7th ed. ed.). Philadelphia: Elsevier/Saunders. ISBN 1437715281. 
  4. ^ Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA (1987). "Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency". Cell 50 (2): 193–202. doi:10.1016/0092-8674(87)90215-7. PMID 3594570. 
  5. ^ van Vliet DN, Brandsma AE, Hartwig NG (2004). "Leukocyte-adhesion deficiency - a rare disorder of inflammation". Ned Tijdschr Geneeskd. 145 (50): 2496–2500. PMID 15638198.