Genetic cause of leukocyte adhesion molecule deficiency. Abnormal splicing and a missense mutation in a conserved region of CD18 impair cell surface expression of beta 2 integrins.
We have identified a type V LAD patient (severe phenotype, and normal size and levels of both CD18 precursor and CD18 mRNA), and determined its molecular basis.
Leukocyte adhesion deficiency (LAD) is an inherited disorder of leukocyte function that is caused by defects in the CD18 gene and is associated with diminished cell surface expression of CD11/CD18 proteins.
Functional studies such as homotypic adhesion and adhesion to a purified counterreceptor for LFA-1, intracellular adhesion molecule-1, demonstrated that LFA-1 function had been restored in the stably transfected LAD patient cell lines.
Functional studies such as homotypic adhesion and adhesion to a purified counterreceptor for LFA-1, intracellular adhesion molecule-1, demonstrated that LFA-1 function had been restored in the stably transfected LAD patient cell lines.
Leukocyte adhesion deficiency (LAD) is an inherited immunodeficiency disease that is characterized by the deficient expression of the leukocyte adhesion glycoproteins lymphocyte function-associated antigen-1 (LFA-1), Mac-1, and p150,95.
Point mutations impairing cell surface expression of the common beta subunit (CD18) in a patient with leukocyte adhesion molecule (Leu-CAM) deficiency.
Lymphocytes from patients with LAD were exposed to CD18-expressing retrovirus and enriched for cells that express CD11a and CD18 (LFA-1) on the cell surface.
In order to study the mechanism of isotype restriction we have analysed specific IgG1, IgG2, IgG3 and IgG4 antibodies directed against a number of different protein and polysaccharide antigens in individuals with HLA class II or LFA-1 deficiency.
On analysis of the CD18 molecular defect in a female Japanese patient with a severe deficiency LAD phenotype, neither CD11a nor CD18 molecules could be detected on the patient's EBV-transformed B lymphoblastoid cell line.
On analysis of the CD18 molecular defect in a female Japanese patient with a severe deficiency LAD phenotype, neither CD11a nor CD18 molecules could be detected on the patient's EBV-transformed B lymphoblastoid cell line.
This amino acid substitution occurs within a highly conserved region of the extracellular domain of CD18 in which several other mutations have been identified in LAD.
This amino acid substitution occurs within a highly conserved region of the extracellular domain of CD18 in which several other mutations have been identified in LAD.
Expression of the LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) antigens on COS cells was not detected, suggesting that these two mutations are sufficient to account for LAD.