Leukocyte adhesion deficiency-1 (LAD1) is a rare and often fatal genetic disorder in humans.
Mechanism [ edit ]
LAD1 is caused by mutations in the ITGB2 gene which are
inherited autorecessively. This gene encodes CD18, a protein present in several cell surface receptor complexes found on white blood cells, including [1 ] lymphocyte function-associated antigen 1 (LFA-1), complement receptor 3 (CR-3), and complement receptor 4 (CR-4). The deficiency of LFA-1 causes neutrophils to be unable to adhere to and migrate out of blood vessels, so their counts can be high. It also impairs immune cell interaction, immune recognition, and cell-killing lymphocyte functions. The lack of CR3 interferes with chemotaxis, phagocytosis, and respiratory burst.
The main sign of the disease is life-threatening, recurrent
bacterial or fungal soft tissue infections. These infections are often apparent at birth and may spread throughout the body. Other signs include delayed separation of the umbilical cord, periodontal disease, elevated neutrophils, and impaired wound healing, but not increased vulnerability to viral infections or cancer. Such patients have fever as the menifestation of infection, inflammatory responses are indolent.
Diagnosis [ edit ]
Flow cytometry with monoclonal antibodies is used to screen for deficiencies of CD18.
Epidemiology [ edit ]
As of 2010
, LAD1 has been observed in several hundred children worldwide.
Treatment [ edit ]
Because the CD18 gene has been cloned and sequenced, this disorder is a potential candidate for gene therapy.
See also [ edit ]
References [ edit ]
^ Etzioni A, Harlan JM. Cell adhesion and leukocyte adhesion defects. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:550–564.
^ Etzioni, A. (2010). "Defects in the leukocyte adhesion cascade". Clinic Rev Allerg Immunol 38 (1): 54–60. doi: 10.1007/s12016-009-8132-3 . Retrieved 09/11/2011.
^ Candotti F, Fischer A. Gene therapy. In: Ochs HD, Smith CIE, Puck JM, eds. Primary immunodeficiency diseases: a molecular and genetic approach. Oxford: Oxford University Press, 2007:688–705.