Integrin subunit beta 2 (ITGB2) (ITGB2)

Integrin subunit beta 2 (ITGB2), also known as CD18, is a critical transmembrane protein that functions as the common beta subunit for the leukocyte adhesion molecule (beta-2 integrin) family (UniProt: P05107). It pairs with different alpha subunits to form heterodimers such as LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), which are essential for leukocytes to adhere to the vascular endothelium and migrate to sites of infection (PubMed: 35045123). Mutations in the ITGB2 gene cause Leukocyte Adhesion Deficiency type I (LAD-I), a rare genetic disorder characterized by life-threatening bacterial and fungal infections due to the inability of neutrophils to exit the bloodstream. In the context of autologous CD34+ hematopoietic stem cell therapy, a functional copy of the ITGB2 gene is delivered ex vivo using a lentiviral vector, such as in the investigational drug Ladervitigene autotemcel (RP-L201). These modified stem cells are then re-infused into the patient, where they engraft in the bone marrow and produce functional leukocytes that express CD18 on their surface. This restoration of ITGB2 expression allows for normal leukocyte trafficking and immune response, providing a potentially curative treatment for LAD-I (Rocket Pharmaceuticals, 2023). Clinical trials have demonstrated that this approach can lead to sustained CD18 expression and a significant reduction in the frequency of severe infections.

Other names

CD18Leukocyte-associated antigen beta subunitCell surface adhesion glycoprotein LFA-1/CR3/p150,95 subunit betaComplement receptor C3 subunit betaLAD1

Gene replacement therapy via lentiviral-mediated transduction of autologous CD34+ hematopoietic stem cells to restore functional ITGB2 protein expression.