Integrin alpha-4 (ITGA4) receptor (ITGA4)

Integrin alpha-4 (ITGA4), also known as CD49d, is a transmembrane glycoprotein that serves as the alpha subunit for two distinct heterodimeric receptors: α4β1 (VLA-4) and α4β7 (UniProt P13612). These receptors are primarily expressed on the surface of leukocytes, where they mediate cell-cell and cell-matrix adhesion by binding to ligands such as Vascular Cell Adhesion Molecule-1 (VCAM-1) and Mucosal Vascular Addressin Cell Adhesion Molecule-1 (MAdCAM-1) (PubMed: 29438608). In the context of inflammatory diseases like Crohn's disease and ulcerative colitis, α4 integrins are critical for the recruitment of inflammatory cells into the intestinal mucosa. The "indirect combination context with infliximab" refers to clinical strategies where anti-integrin therapies (e.g., vedolizumab) are used either sequentially or in combination with TNF-alpha inhibitors like infliximab to treat refractory patients who do not achieve remission with monotherapy (PubMed: 33156108). While infliximab targets systemic inflammation by neutralizing TNF-alpha, α4 integrin antagonists provide a more localized or trafficking-specific approach to reducing leukocyte infiltration. This dual-pathway inhibition is an emerging area of "dual biological therapy" aimed at overcoming therapeutic plateaus in moderate-to-severe autoimmune conditions (PubMed: 34255341). Clinical studies suggest that combining these mechanisms may improve remission rates, though it requires careful monitoring for cumulative immunosuppression and specific risks like Progressive Multifocal Leukoencephalopathy (PML) associated with systemic α4 blockade.

Other names

CD49dVLA-4 alpha subunitAntigen CD49DAlpha-4 integrinITGA4

Antagonism of α4 integrin subunits to prevent the binding of leukocytes to endothelial ligands (VCAM-1 and MAdCAM-1), thereby inhibiting their migration into inflamed tissues. In combination with infliximab, it provides dual inhibition of both leukocyte trafficking and TNF-alpha-mediated cytokine signaling (PubMed: 29438608, PubMed: 33156108).