Heterogeneity in the molecular defect leading to the leukocyte adhesion deficiency*
Leukocyte adhesion deficiency (LAD) is a recessive autosomal disease characterized by life-threatening recurrent bacterial infections, by defective functions of leukocytes and by deficient membrane expression of leukocyte adhesion glycoproteins. These proteins, LFA-1, Mac-1 and p150,95, are al/pl heterodimers composed of different a chains and of a common p chain. Patients with the severe phenotype of the disease completely lack the three glycoproteins on cell surface. Previous studies showed a conserved synthesis of the LFA-1 a chain precursor in cytosol of patients' cells and an inconstant presence of the p chain precursor. When present, precursors are in free form and not associated to a/p complexes in the cells of patients with the severe phenotype. The availability of the p chain cDNA probe allowed us to examine the p chain gene expression in the lymphoblastoid cell lines of 4 patients. On the basis of the results obtained both at protein and RNA levels we can distinguish 3 types of mutations characterized by (a) barely detectable p subunit messenger RNA and undetectable p precursor, (b) decreased level of subunit mRNA and undetectable p precursor and (c) normal p subunit mRNA level and detectable p precursor of normal size.