Integrin beta-2 (ITGB2) (CD18)

Integrin beta-2 (ITGB2), commonly known as CD18, is a critical cell surface receptor that combines with various alpha subunits (CD11a, CD11b, CD11c, or CD11d) to form the beta-2 integrin family, which is essential for leukocyte adhesion and migration. These heterodimers facilitate the stable attachment of white blood cells to the vascular endothelium and their subsequent extravasation into tissues to combat infection. Mutations in the ITGB2 gene lead to Leukocyte Adhesion Deficiency type I (LAD-I), a rare and often fatal primary immunodeficiency characterized by recurrent, life-threatening infections and impaired wound healing due to the inability of neutrophils to reach sites of inflammation. Therapeutic strategies for CD18 focus on two extremes: inhibiting its function with monoclonal antibodies to treat autoimmune or inflammatory conditions, and restoring its expression via gene therapy (such as RP-L201) to treat LAD-I. Recent clinical successes in lentiviral-mediated gene restoration have shown that providing a functional copy of the ITGB2 gene to hematopoietic stem cells can lead to sustained CD18 expression and significant clinical improvement in patients with severe LAD-I (Sources: UniProt P05107; NIH/GARD; Rocket Pharmaceuticals clinical data).

Other names

ITGB2Cell surface adhesion glycoprotein LFA-1/CR3/p150,95 subunit betaComplement receptor C3 subunit betaLCAMBLAD

Gene restoration via lentiviral vector-mediated delivery of a functional ITGB2 gene into autologous hematopoietic stem cells; Monoclonal antibody-mediated inhibition of leukocyte adhesion.