Full Library

Integrins are transmembrane receptors that play a key role in cell adhesion and intracellular signaling. Leukocyte integrins are essential for the recruitment of leukocytes from the vasculature to the tissues and are used as therapeutic targets to modulate inflammation. The monoclonal antibody natalizumab targets the α4 subunit of α4β1 and α4β7 integrins, implicated in the entry of lymphocytes in the central nervous system (CNS) and the gut mucosa, respectively. These integrins are involved in the pathogenesis of multiple sclerosis (MS) and inflammatory bowel disease (IBD) which represent the two approved indications for the use of natalizumab. Vedolizumab selectively targets α4β7 integrin and is approved for the treatment of IBD. Progressive multifocal leukoencephalopathy (PML) is the main infectious complication observed with natalizumab, due to the blockade of α4β1-mediated entry of T lymphocytes in the CNS, leading to decreased immunosurveillance against JC virus (JCV). PML is not observed with vedolizumab, which has no effect on leukocyte trafficking to the CNS. The risk of PML development, a life-threatening disease, is associated with the patient’s JCV serostatus, the use of previous immunosuppression, and treatment duration. No specific treatment exists for PML, and therefore stringent risk stratification and prevention strategies are required during natalizumab therapy.

DOI: 10.1007/978-3-031-11363-5_14