Leukocyte adhesion deficiencies

@article{Hanna2012LeukocyteAD,
  title={Leukocyte adhesion deficiencies},
  author={Suhair Hanna and Amos Etzioni},
  journal={Annals of the New York Academy of Sciences},
  year={2012},
  volume={1250}
}
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… 

Leukocyte Adhesion Deficiency III - When Integrins Activation Fails

While several hundreds of patients with LAD I have been reported, LAD III was described in less than 20 patients, and it was proposed that this group, of all integrins activation disorder, be designated as LADIII.

Leukocyte adhesion deficiencies.

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Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation

It is shown that transfection of the subjects' lymphocytes with KINDLIN3 complementary DNA but not CALDAGGEF1 cDNA reverses the LAD-III defect, restoring integrin-mediated adhesion and migration.

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A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets

Two new LAD cases are reported in which lymphocytes, neutrophils, and platelets share severe defects in β1, β2, and β3 integrin activation, and CalDAG-GEFI is identified as a critical regulator of inside-out integrinactivation in human T lymphocytes.

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A novel dual defect by which a truncated GFTP causes the disease in a new LAD II patient is reported, showing that the truncation renders this GFTP unable to localize to the Golgi, the compartment where it is required.

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