α4 integrin

Class

Anti-integrin monoclonal antibody

Pathway

Leukocyte trafficking (α4 subunit, gut + CNS)

Notes

Broader than α4β7 — also blocks CNS trafficking, hence PML risk / REMS restriction.

α4 integrin is a subunit found on the surface of white blood cells (leukocytes), where it pairs with a second subunit to form adhesion molecules that let circulating immune cells stick to blood vessel walls and cross into tissue. This process, called leukocyte trafficking, is a normal part of immune surveillance but becomes harmful when excessive numbers of immune cells migrate into the brain, spinal cord, or gut and drive inflammation, as occurs in multiple sclerosis and inflammatory bowel disease. Monoclonal antibodies directed against α4 integrin block its ability to bind partner proteins on vessel walls, reducing the entry of immune cells into these tissues and dampening inflammation. Because α4 integrin combines with different partner subunits to form gut-selective and broadly acting adhesion complexes, an antibody that blocks the shared α4 subunit affects trafficking into both the gut and the central nervous system, rather than one site alone. This broader reach extends therapeutic benefit to neurological disease but also removes a layer of immune surveillance within the brain, which carries biological consequences discussed further below. This mechanism broadly matters wherever excessive leukocyte infiltration into a specific organ, rather than systemic immune activation, underlies tissue damage.