title: Can selectin and iNKT cell therapies meet the needs of people with sickle cell disease?
abstract: Recent insights into the pathogenesis of microvascular occlusion downstream of the sickled red cell have revealed new therapeutic targets for sickle cell disease (SCD). After the formation of sickle cells, tissue injury spurs inflammation, which leads to receptor-mediated contacts between sickle cells, leukocytes, and vascular endothelium. Specifically, selectins decelerate sickled red cells and leukocytes in the circulation to facilitate endothelial adhesion and other cell-cell interactions, ultimately leading to vascular occlusion. Invariant NKT (iNKT) cells, activated during reperfusion, generate a broad inflammatory response, which further increases cellular adhesion and vascular occlusion. Novel therapies are in development that target selectins and iNKT cells to prevent or interrupt the vicious cycle of adhesion and inflammation. Although the therapies hold promise for the treatment of SCD, an underappreciated threat to their development is poor access to care for people with SCD. Unless the majority of people with SCD have access to consistent, high-quality care, they will not have the opportunity to participate in a clinical trial or receive any new therapy, regardless of its efficacy.
authors.affiliation: Medical Sciences Institute, Blood Center of Wisconsin; and Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Field
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D002448:Cell Adhesion; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002986:Clinical Trials as Topic; D015195:Drug Design; D042783:Endothelial Cells / Q000166:cytology; D006017:Glycolipids / Q000627:therapeutic use; D006297:Health Services Accessibility; D006801:Humans; D007249:Inflammation; D055611:Natural Killer T-Cells / Q000166:cytology*; D011687:Purines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D019087:Selectins / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006017:Glycolipids; C000611532:NKTT120; D011687:Purines; D011720:Pyrazoles; D019087:Selectins; C430916:regadenoson; C553182:rivipansel