Vedolizumab (anti-integrin) is effective for treatment of ulcerative colitis and Crohn's disease

The integrin superfamily consists of 30 proteins that promote cell-cell or cell-matrix interactions. The name integrins derives from the idea that they coordinate (i.e., "integrate") signals.

All integrins are cell surface proteins composed of 2 polypeptide chains, α and β. Integrins are classified into several subfamilies based on the β chains.



Lymphocyte Trafficking. This video describes how lymphocytes travel through the blood stream and into a lymph node. This video is from: Janeway's Immunobiology, 7th Edition, Murphy, Travers, & Walport. Source: Garland Science.

7 Integrin, a cell adhesion molecule, is present in the form of α4β7 integrin or αEβ7 integrin. α4β7 Integrin is expressed on most leucocytes and is essential for their migration to gut-associated lymphoid tissues by interacting with its primary ligand, mucosal addressin cell adhesion molecule-1, which is preferentially expressed in gut-associated lymphoid tissues.

Vedolizumab is a monoclonal antibody being developed by a subsidiary of Takeda Pharmaceuticals for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α4β7 (LPAM-1, lymphocyte Peyer's patch adhesion molecule 1). Blocking the α4β7 integrin results in gut-selective anti-inflammatory activity by blockade of lymphocyte trafficking.

Sunanda Kane, M.D., a gastroenterologist at Mayo Clinic specializing in the care and evaluation of patients with IBD, discusses two articles recently published in NEJM that found patients with ulcerative colitis or Crohn's disease benefited from treatment with vedolizumab compared with placebo. She discusses how vedolizumab is different than other drugs currently used to treat IBD.



Recruitment of Leukocytes to Sites of Infection can be remembered by the mnemonic: "SIP of wine":

S
electins
Integrins
Penetration of of the basement membrane (BM) by PMN

Selectins are first in the chain of events. They upregulate TNF and IL-1. Integrins cause release of VCAM and VLA.

Adhesion molecules, 3 groups are remembered by the mnemonic SIS:

S
electins
Integrins
Superfamily Ig

References:

http://www.ncbi.nlm.nih.gov/pubmed/21047673
http://www.nejm.org/doi/full/10.1056/NEJMe1307415
http://www.nejm.org/doi/full/10.1056/NEJMoa1215739
http://www.nejm.org/doi/full/10.1056/NEJMoa1215734

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