Leukocyte adhesion deficiencies
Article first published online: 25 JAN 2012
© 2012 New York Academy of Sciences.
Annals of the New York Academy of Sciences
Volume 1250, The Year in Human and Medical Genetics: Inborn Errors of Immunity III pages 50–55, February 2012
How to Cite
Hanna, S. and Etzioni, A. (2012), Leukocyte adhesion deficiencies. Annals of the New York Academy of Sciences, 1250: 50–55. doi: 10.1111/j.1749-6632.2011.06389.x
- Issue published online: 24 FEB 2012
- Article first published online: 25 JAN 2012
- leukocyte adhesion deficiency;
- adhesion cascade;
Leukocyte trafficking from the blood stream to tissues is essential for continuous surveillance of foreign antigens. This dynamic process, designated as the leukocyte adhesion cascade, involves distinct steps. In leukocyte adhesion deficiency (LAD) I the firm adhesion of leukocyte to the endothelium is defective, due to mutations in the beta 2 integrin gene. LAD II is caused by mutations in the fucose transporter specific to the Golgi apparatus, leading to the absence of Sialyl Lewis X—the fucosylated ligand for the selectins—thus affecting the rolling phase, the first phase of the cascade. In LAD III, a primary activation defect occurs in beta integrins 1, 2, and 3. Recently, the genetic basis for LAD III has been revealed to involve mutations in kindlin-3, a newly recognized essential component of integrin activation—the second phase of the adhesion cascade. Until now, no human or animal models of defect in transmigration—the fourth and last phase of the cascade—has been described.