A novel point mutation in CD18 causing the expression of dysfunctional CD11/CD18 leucocyte integrins in a patient with leucocyte adhesion deficiency (LAD)

Leucocyte adhesion deficiency type 1 (LAD-1) is characterized by the incapa city of leucocytes to carry out their adhesion functions via their CD11/CD1 8 antigens, which are also referred to as the leucocyte integrins. The pati ents generally suffer from poor wound healing and recurrent bacterial and f ungal infections. In severe cases, the infections are often systemic and li fe-threatening. A LAD patient (AW) of moderate phenotype has been identifie d but, unlike most other cases, the level of CD11/CD18 antigens on her leuc ocytes are uncharacteristically high for a LAD patient. Molecular analysis revealed that she is a compound heterozygote for CD18 mutations. She has in herited a D231H mutation from her father and a G284S mutation from her moth er. By transfection studies, it was established that the G284S mutation doe s not support CD11/CD18 antigen expression on the cell surface. In contrast , the D231H mutation does not affect CD18 forming integrin heterodimers wit h the CD11 antigens on the cell surface. However, the expressed integrins w ith the D231H mutation are not adhesive to ligands.