Therapeutic anti-integrin (α4 and αL) monoclonal antibodies: Two-edged swords?
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Anti-α4 and anti-αL integrin chain monoclonal antibodies have shown a clear-cut beneficial effect in different animal models of autoimmune and inflammatory disorders as well as in human diseases, including multiple sclerosis, inflammatory bowel disease, and psoriasis. It has been widely assumed that this therapeutic effect is mainly consequence of the blockade of leucocyte adhesion to endothelium, inhibiting thus their extravasation and the inflammatory phenomenon. However, it is evident that both α4β1 (very late antigen-4) and αLβ2 (leucocyte function-associated antigen-1) integrins have additional important roles in other immune phenomena, including the formation of the immune synapse and the differentiation of T helper 1 lymphocytes. Therefore, it is very feasible that the long-term administration of blocking agents directed against these integrins to patients with inflammatory/autoimmune conditions may have undesirable or unexpected effects. © 2005 Blackwell Publishing Ltd.
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Antibody responses; Genetics; Immunoglobulins; Xenotransplantation alpha integrin; alpha4 integrin; efalizumab; intercellular adhesion molecule 1; lymphocyte function associated antigen 1; natalizumab; protein alphaL integrin; unclassified drug; vascular cell adhesion molecule 1; very late activation antigen 4; antibody response; antigen function; autoimmune disease; cell differentiation; clinical trial; drug effect; endothelium; enteritis; extravasation; helper cell; human; inflammation; leukocyte adherence; multiple sclerosis; nonhuman; priority journal; progressive multifocal leukoencephalopathy; psoriasis; review; synaptic transmission; tuberculosis; xenotransplantation; Antibodies, Monoclonal; Autoimmune Diseases; Humans; Inflammation; Integrin alpha4beta1; Lymphocyte Function-Associated Antigen-1
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