Can selectin and iNKT cell therapies meet the needs of people with sickle cell disease? Hematology Am Soc Hematol Educ Program 2015;2015:426-32
Date
12/08/2015Pubmed ID
26637753DOI
10.1182/asheducation-2015.1.426Scopus ID
2-s2.0-85010928634 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Field JJAuthor
Joshua J. Field MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anemia, Sickle CellAntibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Cell Adhesion
Cell- and Tissue-Based Therapy
Clinical Trials as Topic
Drug Design
Endothelial Cells
Glycolipids
Health Services Accessibility
Humans
Inflammation
Natural Killer T-Cells
Purines
Pyrazoles
Selectins
