Following monoclonal antibody is directed against alpha 4 integrin (REPEAT)
**Core Concept**
Monoclonal antibodies targeting alpha 4 integrin are used in the treatment of autoimmune diseases and inflammatory conditions, specifically those involving leukocyte adhesion to endothelial cells. These antibodies work by inhibiting the interaction between alpha 4 integrin on leukocytes and its ligands on endothelial cells, thereby reducing inflammation.
**Why the Correct Answer is Right**
Natalizumab, the correct answer, is a monoclonal antibody that specifically binds to alpha 4 integrin, preventing its interaction with its ligands such as VCAM-1 (Vascular Cell Adhesion Molecule-1) and MAdCAM-1 (Mucosal Vascular Addressin Cell Adhesion Molecule-1). This action inhibits the migration of leukocytes across the endothelial cell layer, leading to reduced inflammation in conditions like multiple sclerosis and Crohn's disease. Natalizumab's mechanism of action is mediated through the inhibition of the alpha 4 integrin/VCAM-1 interaction, which is a key step in leukocyte recruitment to sites of inflammation.
**Why Each Wrong Option is Incorrect**
**Option A:** Infliximab is a monoclonal antibody directed against TNF-alpha, not alpha 4 integrin, and is used in the treatment of rheumatoid arthritis and Crohn's disease.
**Option B:** Vedolizumab is a monoclonal antibody targeting alpha 4 beta 7 integrin, another leukocyte adhesion molecule, but not alpha 4 integrin alone.
**Option C:** Abatacept is a biologic agent that modulates T-cell activation by binding to CD80 and CD86 on antigen-presenting cells, and is not related to alpha 4 integrin.
**Clinical Pearl / High-Yield Fact**
Monoclonal antibodies targeting alpha 4 integrin, such as natalizumab, are associated with an increased risk of progressive multifocal leukoencephalopathy (PML), a rare but serious demyelinating disease of the central nervous system caused by JC virus reactivation.
**Correct Answer:** C.